@article{lee_you_taylor-just_linder_atkins_ralph_cruz_bonner_2022, title={Pulmonary exposure of mice to ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX) suppresses the innate immune response to carbon black nanoparticles and stimulates lung cell proliferation}, ISSN={["1091-7691"]}, DOI={10.1080/08958378.2022.2086651}, abstractNote={Abstract Background Per- and polyfluoroalkyl substances (PFAS) have been associated with respiratory diseases in humans, yet the mechanisms through which PFAS cause susceptibility to inhaled agents is unknown. Herein, we investigated the effects of ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX), an emerging PFAS, on the pulmonary immune response of mice to carbon black nanoparticles (CBNP). We hypothesized that pulmonary exposure to GenX would increase susceptibility to CBNP through suppression of innate immunity. Methods Male C57BL/6 mice were exposed to vehicle, 4 mg/kg CBNP, 10 mg/kg GenX, or CBNP and GenX by oropharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) was collected at 1 and 14 days postexposure for cytokines and total protein. Lung tissue was harvested for histopathology, immunohistochemistry (Ki67 and phosphorylated (p)-STAT3), western blotting (p-STAT3 and p-NF-κB), and qRT-PCR for cytokine mRNAs. Results CBNP increased CXCL-1 and neutrophils in BALF at both time points evaluated. However, GenX/CBNP co-exposure reduced CBNP-induced CXCL-1 and neutrophils in BALF. Moreover, CXCL-1, CXCL-2 and IL-1β mRNAs were increased by CBNP in lung tissue but reduced by GenX. Western blotting showed that CBNP induced p-NF-κB in lung tissue, while the GenX/CBNP co-exposed group displayed decreased p-NF-κB. Furthermore, mice exposed to GenX or GenX/CBNP displayed increased numbers of BALF macrophages undergoing mitosis and increased Ki67 immunostaining. This was correlated with increased p-STAT3 by western blotting and immunohistochemistry in lung tissue from mice co-exposed to GenX/CBNP. Conclusions Pulmonary exposure to GenX suppressed CBNP-induced innate immune response in the lungs of mice yet promoted the proliferation of macrophages and lung epithelial cells.}, journal={INHALATION TOXICOLOGY}, author={Lee, Ho Young and You, Dorothy J. and Taylor-Just, Alexia J. and Linder, Keith E. and Atkins, Hannah M. and Ralph, Lauren M. and Cruz, Gabriela and Bonner, James C.}, year={2022}, month={Jun} }
 @article{you_lee_taylor-just_bonner_2022, title={Synergistic induction of IL-6 production in human bronchial epithelial cells in vitro by nickel nanoparticles and lipopolysaccharide is mediated by eSTAT3 and C/EBP beta}, volume={83}, ISSN={["1879-3177"]}, DOI={10.1016/j.tiv.2022.105394}, abstractNote={We previously reported that delivery of nickel nanoparticles (NiNPs) and bacterial lipopolysaccharide (LPS) into the lungs of mice synergistically increased IL-6 production and inflammation, and male mice were more susceptible than female mice. The primary goal of this study was to utilize an in vitro human lung epithelial cell model (BEAS-2B) to investigate the intracellular signaling mechanisms that mediate IL-6 production by LPS and NiNPs. We also investigated the effect of sex hormones on NiNP and LPS-induced IL-6 production in vitro. LPS and NiNPs synergistically induced IL-6 mRNA and protein in BEAS-2B cells. TPCA-1, a dual inhibitor of IKK-2 and STAT3, blocked the synergistic increase in IL-6 caused by LPS and NiNPs, abolished STAT3 activation, and reduced C/EBPβ. Conversely, SC144, an inhibitor of the gp130 component of the IL-6 receptor, enhanced IL-6 production induced by LPS and NiNPs. Treatment of BEAS-2B cells with sex hormones (17β-estradiol, progesterone, or testosterone) or the anti-oxidant NAC, had no effect on IL-6 induction by LPS and NiNPs. These data suggest that LPS and NiNPs induce IL-6 via STAT3 and C/EBPβ in BEAS-2B cells. While BEAS-2B cells are a suitable model to study mechanisms of IL-6 production, they do not appear to be suitable for studying the effect of sex hormones.}, journal={TOXICOLOGY IN VITRO}, author={You, Dorothy J. and Lee, Ho Young and Taylor-Just, Alexia J. and Bonner, James C.}, year={2022}, month={Sep} }
 @article{sridharan_taylor-just_bonner_2021, title={Osteopontin mRNA expression by rat mesothelial cells exposed to multi-walled carbon nanotubes as a potential biomarker of chronic neoplastic transformation in vitro}, volume={73}, ISSN={["1879-3177"]}, DOI={10.1016/j.tiv.2021.105126}, abstractNote={Mesothelioma is a cancer of the lung pleura primarily associated with inhalation of asbestos fibers. Multi-walled carbon nanotubes (MWCNTs) are engineered nanomaterials that pose a potential risk for mesothelioma due to properties that are similar to asbestos. Inhaled MWCNTs migrate to the pleura in rodents and some types cause mesothelioma. Like asbestos, there is a diversity of MWCNT types. We investigated the neoplastic potential of tangled (tMWCNT) versus rigid (rMWCNT) after chronic exposure using serial passages of rat mesothelial cells in vitro. Normal rat mesothelial (NRM2) cells were exposed to tMWCNTs or rMWCNTs for 45 weeks over 85 passages to determine if exposure resulted in transformation to a neoplastic phenotype. Rat mesothelioma (ME1) cells were used as a positive control. Osteopontin (OPN) mRNA was assayed as a biomarker of transformation by real time quantitative polymerase chain reaction (qPCR) and transformation was determined by a cell invasion assay. Exposure to rMWCNTs, but not tMWCNTs, resulted in transformation of NRM2 cells into an invasive phenotype that was similar to ME1 cells. Moreover, exposure of NRM2 cells to rMWCNTs increased OPN mRNA that correlated with cellular transformation. These data suggest that OPN is a potential biomarker that should be further investigated to screen the carcinogenicity of MWCNTs in vitro.}, journal={TOXICOLOGY IN VITRO}, author={Sridharan, Sreepradha and Taylor-Just, Alexia and Bonner, James C.}, year={2021}, month={Jun} }
 @article{ihrie_duke_shipkowski_you_lee_taylor-just_bonner_2021, title={STAT6-dependent exacerbation of house dust mite-induced allergic airway disease in mice by multi-walled carbon nanotubes}, volume={22}, ISSN={["2452-0748"]}, DOI={10.1016/j.impact.2021.100309}, abstractNote={There is increasing evidence that inhaled multi-walled carbon nanotubes (MWCNTs) can have harmful effects on the respiratory system. Rodent studies suggest that individuals with asthma may be susceptible to the adverse pulmonary effects of MWCNTs. Asthma is an allergic lung disease characterized by a TH2 immune response that results in chronic airway disease characterized by eosinophilic lung inflammation, airway mucous cell metaplasia, and airway fibrosis. Signal transducer and activator of transcription 6 (STAT6) is a transcription factor with multiple roles in TH2 type inflammation. Herein we sought to examine the role of STAT6 in the exacerbation of house dust mite (HDM) allergen-induced allergic airway disease by MWCNTs. Male wild type (WT) and STAT6 knockout (Stat6 KO) mice were dosed via intranasal aspiration on days 0, 2, 4, 14, 16 and 18 with either vehicle, HDM extract, MWCNTs, or a combination of HDM and MWCNTs. Necropsy was performed on day 21 to collect bronchoalveolar lavage fluid (BALF), serum and lung tissue. MWCNTs exacerbated HDM-induced allergic endpoints, including eosinophilic lung inflammation, mucous cell metaplasia, and serum IgE levels. HDM-induced eosinophilic lung inflammation, mucous cell metaplasia, and serum IgE and exacerbation of these endpoints by MWCNTs were ablated in Stat6 KO mice. In addition, airway fibrosis was significantly increased by the combination of HDM and MWCNTs in WT mice but not in Stat6 KO mice. These findings provide new mechanistic insight by demonstrating a requirement for STAT6 in MWCNT-induced exacerbation of allergic respiratory disease.}, journal={NANOIMPACT}, author={Ihrie, Mark D. and Duke, Katherine S. and Shipkowski, Kelly A. and You, Dorothy J. and Lee, Ho Young and Taylor-Just, Alexia J. and Bonner, James C.}, year={2021}, month={Apr} }
 @article{you_lee_taylor-just_linder_bonner_2020, title={Sex differences in the acute and subchronic lung inflammatory responses of mice to nickel nanoparticles}, volume={14}, ISSN={["1743-5404"]}, DOI={10.1080/17435390.2020.1808105}, abstractNote={Abstract Nickel nanoparticles (NiNPs) are increasingly used in nanotechnology applications, yet information on sex differences in NiNP-induced lung disease is lacking. The goal of this study was to explore mechanisms of susceptibility between male and female mice after acute or subchronic pulmonary exposure to NiNPs. For acute exposure, male and female mice received a single dose of NiNPs with or without LPS by oropharyngeal aspiration and were necropsied 24 h later. For subchronic exposure, mice received NiNPs with or without LPS six times over 3 weeks prior to necropsy. After acute exposure to NiNPs and LPS, male mice had elevated cytokines (CXCL1 and IL-6) and more neutrophils in bronchoalveolar lavage fluid (BALF), along with greater STAT3 phosphorylation in lung tissue. After subchronic exposure to NiNPs and LPS, male mice exhibited increased monocytes in BALF. Moreover, subchronic exposure of male mice to NiNP only induced higher CXCL1 and CCL2 in BALF along with increased alveolar infiltrates and CCL2 in lung tissue. STAT1 in lung tissue was induced by subchronic exposure to NiNPs in females but not males. Males had a greater induction of IL-6 mRNA in liver after acute exposure to NiNPs and LPS, and greater CCL2 mRNA in liver after subchronic NiNP exposure. These data indicate that susceptibility of males to acute lung inflammation involves enhanced neutrophilia with increased CXCL1 and IL-6/STAT3 signaling, whereas susceptibility to subchronic lung inflammation involves enhanced monocytic infiltration with increased CXCL1 and CCL2. STAT transcription factors appear to play a role in these sex differences. This study demonstrates sex differences in the lung inflammatory response of mice to NiNPs that has implications for human disease.}, number={8}, journal={NANOTOXICOLOGY}, author={You, Dorothy J. and Lee, Ho Young and Taylor-Just, Alexia J. and Linder, Keith E. and Bonner, James C.}, year={2020}, month={Sep}, pages={1058–1081} }
 @article{taylor-just_ihrie_duke_lee_you_hussain_kodali_ziemann_creutzenberg_vulpoi_et al._2020, title={The pulmonary toxicity of carboxylated or aminated multi-walled carbon nanotubes in mice is determined by the prior purification method}, volume={17}, ISSN={["1743-8977"]}, DOI={10.1186/s12989-020-00390-y}, abstractNote={Abstract}, number={1}, journal={PARTICLE AND FIBRE TOXICOLOGY}, author={Taylor-Just, Alexia J. and Ihrie, Mark D. and Duke, Katherine S. and Lee, Ho Young and You, Dorothy J. and Hussain, Salik and Kodali, Vamsi K. and Ziemann, Christina and Creutzenberg, Otto and Vulpoi, Adriana and et al.}, year={2020}, month={Dec} }
 @article{ihrie_taylor-just_walker_stout_gupta_richey_hayden_baker_sparrow_duke_et al._2019, title={Inhalation exposure to multi-walled carbon nanotubes alters the pulmonary allergic response of mice to house dust mite allergen}, volume={31}, ISSN={["1091-7691"]}, DOI={10.1080/08958378.2019.1643955}, abstractNote={Abstract Background: Increasing evidence from rodent studies indicates that inhaled multi-walled carbon nanotubes (MWCNTs) have harmful effects on the lungs. In this study, we examined the effects of inhalation exposure to MWCNTs on allergen-induced airway inflammation and fibrosis. We hypothesized that inhalation pre-exposure to MWCNTs would render mice susceptible to developing allergic lung disease induced by house dust mite (HDM) allergen. Methods: Male B6C3F1/N mice were exposed by whole-body inhalation for 6 h a day, 5 d a week, for 30 d to air control or 0.06, 0.2, and 0.6 mg/m3 of MWCNTs. The exposure atmospheres were agglomerates (1.4–1.8 µm) composed of MWCNTs (average diameter 16 nm; average length 2.4 µm; 0.52% Ni). Mice then received 25 µg of HDM extract by intranasal instillation 6 times over 3 weeks. Necropsy was performed at 3 and 30 d after the final HDM dose to collect serum, bronchoalveolar lavage fluid (BALF), and lung tissue for histopathology. Results: MWCNT exposure at the highest dose inhibited HDM-induced serum IgE levels, IL-13 protein levels in BALF, and airway mucus production. However, perivascular and peribronchiolar inflammatory lesions were observed in the lungs of mice at 3 d with MWCNT and HDM, but not MWCNT or HDM alone. Moreover, combined HDM and MWCNT exposure increased airway fibrosis in the lungs of mice. Conclusions: Inhalation pre-exposure to MWCNTs inhibited HDM-induced TH2 immune responses, yet this combined exposure resulted in vascular inflammation and airway fibrosis, indicating that MWCNT pre-exposure alters the immune response to allergens.}, number={5}, journal={INHALATION TOXICOLOGY}, author={Ihrie, Mark D. and Taylor-Just, Alexia J. and Walker, Nigel J. and Stout, Matthew D. and Gupta, Amit and Richey, Jamie S. and Hayden, Barry K. and Baker, Gregory L. and Sparrow, Barney R. and Duke, Katherine S. and et al.}, year={2019}, month={Apr}, pages={192–202} }
 @article{hilton_taylor_hussain_dandley_griffith_garantziotis_parsons_bonner_bereman_2017, title={Mapping differential cellular protein response of mouse alveolar epithelial cells to multi-walled carbon nanotubes as a function of atomic layer deposition coating}, volume={11}, ISSN={["1743-5404"]}, DOI={10.1080/17435390.2017.1299888}, abstractNote={Abstract Carbon nanotubes (CNTs), a prototypical engineered nanomaterial, have been increasingly manufactured for a variety of novel applications over the past two decades. However, since CNTs possess fiber-like shape and cause pulmonary fibrosis in rodents, there is concern that mass production of CNTs will lead to occupational exposure and associated pulmonary diseases. The aim of this study was to use contemporary proteomics to investigate the mechanisms of cellular response in E10 mouse alveolar epithelial cells in vitro after exposure to multi-walled CNTs (MWCNTs) that were functionalized by atomic layer deposition (ALD). ALD is a method used to generate highly uniform and conformal nanoscale thin-film coatings of metals to enhance novel conductive properties of CNTs. We hypothesized that specific types of metal oxide coatings applied to the surface of MWCNTs by ALD would determine distinct proteomic profiles in mouse alveolar epithelial cells in vitro that could be used to predict oxidative stress and pulmonary inflammation. Uncoated (U)-MWCNTs were functionalized by ALD with zinc oxide (ZnO) to yield Z-MWCNTs or aluminum oxide (Al2O3) to yield A-MWCNTs. Significant differential protein expression was found in the following critical pathways: mTOR/eIF4/p70S6K signaling and Nrf-2 mediated oxidative stress response increased following exposure to Z-MWCNTs, interleukin-1 signaling increased following U-MWCNT exposure, and inhibition of angiogenesis by thrombospondin-1, oxidative phosphorylation, and mitochondrial dysfunction increased following A-MWCNT exposure. This study demonstrates that specific types of metal oxide thin film coatings applied by ALD produce distinct cellular and biochemical responses related to lung inflammation and fibrosis compared to uncoated MWCNT exposure in vitro.}, number={3}, journal={NANOTOXICOLOGY}, author={Hilton, Gina M. and Taylor, Alexia J. and Hussain, Salik and Dandley, Erinn C. and Griffith, Emily H. and Garantziotis, Stavros and Parsons, Gregory N. and Bonner, James C. and Bereman, Michael S.}, year={2017}, month={Apr}, pages={313–326} }
 @article{duke_taylor-just_ihrie_shipkowski_thompson_dandley_parsons_bonner_2017, title={STAT1-dependent and -independent pulmonary allergic and fibrogenic responses in mice after exposure to tangled versus rod-like multi-walled carbon nanotubes}, volume={14}, ISSN={["1743-8977"]}, DOI={10.1186/s12989-017-0207-3}, abstractNote={Pulmonary toxicity of multi-walled carbon nanotubes (MWCNTs) is influenced by physicochemical characteristics and genetic susceptibility. We hypothesized that contrasting rigidities of tangled (t) versus rod-like (r) MWCNTs would result in differing immunologic or fibrogenic responses in mice and that these responses would be exaggerated in transgenic mice lacking the signal transducer and activator of transcription-1 (STAT1), a susceptible mouse model of pulmonary fibrosis.Male wild type (Stat1 +/+ ) and STAT1-deficient (Stat1 -/- ) mice were exposed to 4 mg/kg tMWCNTs, rMWCNTs, or vehicle alone via oropharyngeal aspiration and evaluated for inflammation at one and 21 days post-exposure via histopathology, differential cell counts, and cytokine levels in bronchoalveolar lavage fluid (BALF). Granuloma formation, mucous cell metaplasia, and airway fibrosis were evaluated by quantitative morphometry. Airway epithelial cell proliferation was assessed by bromodeoxyuridine (BrdU) incorporation. Cytokine protein levels in BALF and serum IgE levels were measured by ELISA. Lung protein Smad2/3 levels and activation were measured by Western blot. Lung mRNAs were measured by PCR.There was a 7-fold difference in rigidity between tMWCNTs and rMWCNTs as determined by static bending ratio. Both MWCNT types resulted in acute inflammation (neutrophils in BALF) after one-day post-exposure, yet only rMWCNTs resulted in chronic inflammation at 21 days as indicated by neutrophil influx and larger granulomas. Both MWCNTs induced BrdU uptake in airway epithelial cells, with the greatest proliferative response observed in rMWCNT-exposed mice after one-day. Only rMWCNTs induced mucous cell metaplasia, but this index was not different between genotypes. Stat1 -/- mice had higher levels of baseline serum IgE than Stat1 +/+ mice. Greater airway fibrosis was observed with rMWCNTs compared to tMWCNTs, and exaggerated airway fibrosis was seen in the Stat1 -/- mouse lungs with rMWCNTs but not tMWCNTs. Increased fibrosis correlated with elevated levels of TGF-β1 protein levels in the BALF of Stat1 -/- mice exposed to rMWCNTs and increased lung Smad2/3 phosphorylation.Rigidity plays a key role in the toxicity of MWCNTs and results in increased inflammatory, immunologic, and fibrogenic effects in the lung. STAT1 is an important protective factor in the fibroproliferative response to rMWCNTs, regulating both induced TGF-β1 production and Smad2/3 phosphorylation status. Therefore, both rigidity and genetic susceptibility should be major considerations for risk assessment of MWCNTs.}, journal={PARTICLE AND FIBRE TOXICOLOGY}, author={Duke, Katherine S. and Taylor-Just, Alexia J. and Ihrie, Mark D. and Shipkowski, Kelly A. and Thompson, Elizabeth A. and Dandley, Erinn C. and Parsons, Gregory N. and Bonner, James C.}, year={2017}, month={Jul} }
 @article{dandley_taylor_duke_ihrie_shipkowski_parsons_bonner_2016, title={Atomic layer deposition coating of carbon nanotubes with zinc oxide causes acute phase immune responses in human monocytes in vitro and in mice after pulmonary exposure}, volume={13}, ISSN={["1743-8977"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000378430800002&KeyUID=WOS:000378430800002}, DOI={10.1186/s12989-016-0141-9}, abstractNote={Atomic layer deposition (ALD) is a method for applying conformal nanoscale coatings on three-dimensional structures. We hypothesized that surface functionalization of multi-walled carbon nanotubes (MWCNTs) with polycrystalline ZnO by ALD would alter pro-inflammatory cytokine expression by human monocytes in vitro and modulate the lung and systemic immune response following oropharyngeal aspiration in mice.Pristine (U-MWCNTs) were coated with alternating doses of diethyl zinc and water over increasing ALD cycles (10 to 100 ALD cycles) to yield conformal ZnO-coated MWCNTs (Z-MWCNTs). Human THP-1 monocytic cells were exposed to U-MWCNTs or Z-MWCNTs in vitro and cytokine mRNAs measured by Taqman real-time RT-PCR. Male C57BL6 mice were exposed to U- or Z-MWCNTs by oropharyngeal aspiration (OPA) and lung inflammation evaluated at one day post-exposure by histopathology, cytokine expression and differential counting of cells in bronchoalveolar lavage fluid (BALF) cells. Lung fibrosis was evaluated at 28 days. Cytokine mRNAs (IL-6, IL-1β, CXCL10, TNF-α) in lung, heart, spleen, and liver were quantified at one and 28 days. DNA synthesis in lung tissue was measured by bromodeoxyuridine (BrdU) uptake.ALD resulted in a conformal coating of MWCNTs with ZnO that increased proportionally to the number of coating cycles. Z-MWCNTs released Zn(+2) ions in media and increased IL-6, IL-1β, CXCL10, and TNF-α mRNAs in THP-1 cells in vitro. Mice exposed to Z-MWCNTs by OPA had exaggerated lung inflammation and a 3-fold increase in monocytes and neutrophils in BALF compared to U-MWCNTs. Z-MWCNTs, but not U-MWCNTs, induced IL-6 and CXCL10 mRNA and protein in the lungs of mice and increased IL-6 mRNA in heart and liver. U-MWCNTs but not Z-MWCNTs stimulated airway epithelial DNA synthesis in vivo. Lung fibrosis at 28 days was not significantly different between mice treated with U-MWCNT or Z-MWCNT.Pulmonary exposure to ZnO-coated MWCNTs produces a systemic acute phase response that involves the release of Zn(+2), lung epithelial growth arrest, and increased IL-6. ALD functionalization with ZnO generates MWCNTs that possess increased risk for human exposure.}, journal={PARTICLE AND FIBRE TOXICOLOGY}, author={Dandley, Erinn C. and Taylor, Alexia J. and Duke, Katherine S. and Ihrie, Mark D. and Shipkowski, Kelly A. and Parsons, Gregory N. and Bonner, James C.}, year={2016}, month={Jun} }
 @article{hussain_ji_taylor_degraff_george_tucker_chang_li_bonner_garantziotis_2016, title={Multiwalled Carbon Nanotube Functionalization with High Molecular Weight Hyaluronan Significantly Reduces Pulmonary Injury}, volume={10}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.6b03013}, abstractNote={Commercialization of multiwalled carbon nanotubes (MWCNT)-based applications has been hampered by concerns regarding their lung toxicity potential. Hyaluronic acid (HA) is a ubiquitously found polysaccharide, which is anti-inflammatory in its native high molecular weight form. HA-functionalized smart MWCNTs have shown promise as tumor-targeting drug delivery agents and can enhance bone repair and regeneration. However, it is unclear whether HA functionalization could reduce the pulmonary toxicity potential of MWCNTs. Using in vivo and in vitro approaches, we investigated the effectiveness of MWCNT functionalization with HA in increasing nanotube biocompatibility and reducing lung inflammatory and fibrotic effects. We utilized three-dimensional cultures of differentiated primary human bronchial epithelia to translate findings from rodent assays to humans. We found that HA functionalization increased stability and dispersion of MWCNTs and reduced postexposure lung inflammation, fibrosis, and mucus cell metaplasia compared with nonfunctionalized MWCNTs. Cocultures of fully differentiated bronchial epithelial cells (cultivated at air-liquid interface) and human lung fibroblasts (submerged) displayed significant reduction in injury, oxidative stress, as well as pro-inflammatory gene and protein expression after exposure to HA-functionalized MWCNTs compared with MWCNTs alone. In contrast, neither type of nanotubes stimulated cytokine production in primary human alveolar macrophages. In aggregate, our results demonstrate the effectiveness of HA functionalization as a safer design approach to eliminate MWCNT-induced lung injury and suggest that HA functionalization works by reducing MWCNT-induced epithelial injury.}, number={8}, journal={ACS NANO}, author={Hussain, Salik and Ji, Zhaoxia and Taylor, Alexia J. and DeGraff, Laura M. and George, Margaret and Tucker, Charles J. and Chang, Chong Hyun and Li, Ruibin and Bonner, James C. and Garantziotis, Stavros}, year={2016}, month={Aug}, pages={7675–7688} }
 @article{shipkowski_taylor_thompson_glista-baker_sayers_messenger_bauer_jaspers_bonner_2015, title={An allergic lung microenvironment suppresses carbon nanotube-induced inflammasome activation via STAT6-dependent inhibition of caspase-1}, volume={10}, number={6}, journal={PLoS One}, author={Shipkowski, K. A. and Taylor, A. J. and Thompson, E. A. and Glista-Baker, E. E. and Sayers, B. C. and Messenger, Z. J. and Bauer, R. N. and Jaspers, I. and Bonner, J. C.}, year={2015} }
 @article{thompson_sayers_glista-baker_shipkowski_ihrie_duke_taylor_bonner_2015, title={Role of Signal Transducer and Activator of Transcription 1 in Murine Allergen-Induced Airway Remodeling and Exacerbation by Carbon Nanotubes}, volume={53}, ISSN={["1535-4989"]}, DOI={10.1165/rcmb.2014-0221oc}, abstractNote={Asthma is characterized by a T helper type 2 phenotype and by chronic allergen-induced airway inflammation (AAI). Environmental exposure to air pollution ultrafine particles (i.e., nanoparticles) exacerbates AAI, and a concern is possible exacerbation posed by engineered nanoparticles generated by emerging nanotechnologies. Signal transducer and activator of transcription (STAT) 1 is a transcription factor that maintains T helper type 1 cell development. However, the role of STAT1 in regulating AAI or exacerbation by nanoparticles has not been explored. In this study, mice with whole-body knockout of the Stat1 gene (Stat1(-/-)) or wild-type (WT) mice were sensitized to ovalbumin (OVA) allergen and then exposed to multiwalled carbon nanotubes (MWCNTs) by oropharygneal aspiration. In Stat1(-/-) and WT mice, OVA increased eosinophils in bronchoalveolar lavage fluid, whereas MWCNTs increased neutrophils. Interestingly, OVA sensitization prevented MWCNT-induced neutrophilia and caused only eosinophilic inflammation. Stat1(-/-) mice displayed increased IL-13 in bronchoalveolar lavage fluid at 1 day compared with WT mice after treatment with OVA or OVA and MWCNTs. At 21 days, the lungs of OVA-sensitized Stat1(-/-) mice displayed increased eosinophilia, goblet cell hyperplasia, airway fibrosis, and subepithelial apoptosis. MWCNTs further increased OVA-induced goblet cell hyperplasia, airway fibrosis, and apoptosis in Stat1(-/-) mice at 21 days. These changes corresponded to increased levels of profibrogenic mediators (transforming growth factor-β1, TNF-α, osteopontin) but decreased IL-10 in Stat1(-/-) mice. Finally, fibroblasts isolated from the lungs of Stat1(-/-) mice produced significantly more collagen mRNA and protein in response to transforming growth factor-β1 compared with WT lung fibroblasts. Our results support a protective role for STAT1 in chronic AAI and exacerbation of remodeling caused by MWCNTs.}, number={5}, journal={AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY}, author={Thompson, Elizabeth A. and Sayers, Brian C. and Glista-Baker, Ellen E. and Shipkowski, Kelly A. and Ihrie, Mark D. and Duke, Katherine S. and Taylor, Alexia J. and Bonner, James C.}, year={2015}, month={Nov}, pages={625–636} }
 @article{hilton_taylor_mcclure_parsons_bonner_bereman_2015, title={Toxicoproteomic analysis of pulmonary carbon nanotube exposure using LC-MS/MS}, volume={329}, ISSN={["0300-483X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000350519500009&KeyUID=WOS:000350519500009}, DOI={10.1016/j.tox.2015.01.011}, abstractNote={Toxicoproteomics is a developing field that utilizes global proteomic methodologies to investigate the physiological response as a result of adverse toxicant exposure. The aim of this study was to compare the protein secretion profile in lung bronchoalveolar lavage fluid (BALF) from mice exposed to non-functionalized multi-walled carbon nanotubes (U-MWCNTs) or MWCNTs functionalized by nanoscale Al2O3 coatings (A-MWCNT) formed using atomic layer deposition (ALD). Proteins were identified using liquid chromatography tandem mass spectrometry (LC-MS/MS), and quantified using a combination of two label-free proteomic methods: spectral counting and MS1 peak area analysis. On average 465 protein groups were identified per sample and proteins were first screened using spectral counting and the Fisher’s exact test to determine differentially regulated species. Significant proteins by Fisher’s exact test (p < 0.05) were then verified by integrating the intensity under the extracted ion chromatogram from a single unique peptide for each protein across all runs. A two sample t-test based on integrated peak intensities discovered differences in 27 proteins for control versus U-MWCNT, 13 proteins for control versus A-MWCNT, and 2 proteins for U-MWCNT versus A-MWCNT. Finally, an in-vitro binding experiment was performed yielding 4 common proteins statistically different (p < 0.05) for both the in-vitro and in-vivo study. Several of the proteins found to be significantly different between exposed and control groups are known to play a key role in inflammatory and immune response. A comparison between the in-vitro and in-vivo CNT exposure emphasized a true biological response to CNT exposure.}, journal={TOXICOLOGY}, author={Hilton, Gina M. and Taylor, Alexia J. and McClure, Christina D. and Parsons, Gregory N. and Bonner, James C. and Bereman, Michael S.}, year={2015}, month={Mar}, pages={80–87} }
 @article{taylor_mcclure_shipkowski_thompson_hussain_garantziotis_parsons_bonner_2014, title={Atomic Layer Deposition Coating of Carbon Nanotubes with Aluminum Oxide Alters Pro-Fibrogenic Cytokine Expression by Human Mononuclear Phagocytes In Vitro and Reduces Lung Fibrosis in Mice In Vivo}, volume={9}, ISSN={["1932-6203"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000341774300028&KeyUID=WOS:000341774300028}, DOI={10.1371/journal.pone.0106870}, abstractNote={Background Multi-walled carbon nanotubes (MWCNTs) pose a possible human health risk for lung disease as a result of inhalation exposure. Mice exposed to MWCNTs develop pulmonary fibrosis. Lung macrophages engulf MWCNTs and produce pro-fibrogenic cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and osteopontin (OPN). Atomic layer deposition (ALD) is a novel process used to enhance functional properties of MWCNTs, yet the consequence of ALD-modified MWCNTs on macrophage biology and fibrosis is unknown. Methods The purpose of this study was to determine whether ALD coating with aluminum oxide (Al2O3) would alter the fibrogenic response to MWCNTs and whether cytokine expression in human macrophage/monocytes exposed to MWCNTs in vitro would predict the severity of lung fibrosis in mice. Uncoated (U)-MWCNTs or ALD-coated (A)-MWCNTs were incubated with THP-1 macrophages or human peripheral blood mononuclear cells (PBMC) and cell supernatants assayed for cytokines by ELISA. C57BL6 mice were exposed to a single dose of A- or U-MWCNTs by oropharyngeal aspiration (4 mg/kg) followed by evaluation of histopathology, lung inflammatory cell counts, and cytokine levels at day 1 and 28 post-exposure. Results ALD coating of MWCNTs with Al2O3 enhanced IL-1β secretion by THP-1 and PBMC in vitro, yet reduced protein levels of IL-6, TNF-α, and OPN production by THP-1 cells. Moreover, Al2O3 nanoparticles, but not carbon black NPs, increased IL-1β but decreased OPN and IL-6 in THP-1 and PBMC. Mice exposed to U-MWCNT had increased levels of all four cytokines assayed and developed pulmonary fibrosis by 28 days, whereas ALD-coating significantly reduced fibrosis and cytokine levels at the mRNA or protein level. Conclusion These findings indicate that ALD thin film coating of MWCNTs with Al2O3 reduces fibrosis in mice and that in vitro phagocyte expression of IL-6, TNF-α, and OPN, but not IL-1β, predict MWCNT-induced fibrosis in the lungs of mice in vivo.}, number={9}, journal={PLOS ONE}, author={Taylor, Alexia J. and McClure, Christina D. and Shipkowski, Kelly A. and Thompson, Elizabeth A. and Hussain, Salik and Garantziotis, Stavros and Parsons, Gregory N. and Bonner, James C.}, year={2014}, month={Sep} }
 @article{glista-baker_taylor_sayers_thompson_bonner_2014, title={Nickel Nanoparticles cause exaggerated lung and airway remodeling in mice lacking the T-box transcription factor, TBX21 (T-bet)}, volume={11}, journal={Particle and Fibre Toxicology}, author={Glista-Baker, E. E. and Taylor, A. J. and Sayers, B. C. and Thompson, E. A. and Bonner, J. C.}, year={2014} }
 @article{interlaboratory evaluation of in vitro cytotoxicity and inflammatory responses to engineered n nanomaterials: the niehs nano go consortium_2013, volume={121}, number={6}, journal={Environmental Health Perspectives}, year={2013}, pages={683–690} }
 @article{interlaboratory evaluation of rodent pulmonary responses to engineered nanomaterials: the niehs nano go consortium_2013, volume={121}, number={6}, journal={Environmental Health Perspectives}, year={2013}, pages={676–682} }
 @article{sayers_taylor_glista-baker_shipley-phillips_dackor_edin_lih_tomer_zeldin_langenbach_et al._2013, title={Role of Cyclooxygenase-2 in Exacerbation of Allergen-Induced Airway Remodeling by Multiwalled Carbon Nanotubes}, volume={49}, ISSN={["1535-4989"]}, DOI={10.1165/rcmb.2013-0019oc}, abstractNote={The emergence of nanotechnology has produced a multitude of engineered nanomaterials such as carbon nanotubes (CNTs), and concerns have been raised about their effects on human health, especially for susceptible populations such as individuals with asthma. Multiwalled CNTs (MWCNTs) have been shown to exacerbate ovalbumin (OVA)-induced airway remodeling in mice. Moreover, cyclooxygenase-2 (COX-2) has been described as a protective factor in asthma. We postulated that COX-2-deficient (COX-2(-/-)) mice would be susceptible to MWCNT-induced exacerbations of allergen-induced airway remodeling, including airway inflammation, fibrosis, and mucus-cell metaplasia (i.e., the formation of goblet cells). Wild-type (WT) or COX-2(-/-) mice were sensitized to OVA to induce allergic airway inflammation before a single dose of MWCNTs (4 mg/kg) delivered to the lungs by oropharyngeal aspiration. MWCNTs significantly increased OVA-induced lung inflammation and mucus-cell metaplasia in COX-2(-/-) mice compared with WT mice. However, airway fibrosis after exposure to allergen and MWCNTs was no different between WT and COX-2(-/-) mice. Concentrations of certain prostanoids (prostaglandin D2 and thromboxane B2) were enhanced by OVA or MWCNTs in COX-2(-/-) mice. No differences in COX-1 mRNA concentrations were evident between WT and COX-2(-/-) mice treated with OVA and MWCNTs. Interestingly, MWCNTs significantly enhanced allergen-induced cytokines involved in Th2 (IL-13 and IL-5), Th1 (CXCL10), and Th17 (IL-17A) inflammatory responses in COX-2(-/-) mice, but not in WT mice. We conclude that exacerbations of allergen-induced airway inflammation and mucus-cell metaplasia by MWCNTs are enhanced by deficiencies in COX-2, and are associated with the activation of a mixed Th1/Th2/Th17 immune response.}, number={4}, journal={AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY}, author={Sayers, Brian C. and Taylor, Alexia J. and Glista-Baker, Ellen E. and Shipley-Phillips, Jeanette K. and Dackor, Ryan T. and Edin, Matthew L. and Lih, Fred B. and Tomer, Kenneth B. and Zeldin, Darryl C. and Langenbach, Robert and et al.}, year={2013}, month={Oct}, pages={525–535} }
 @article{glista-baker_taylor_sayers_thompson_bonner_2012, title={Nickel Nanoparticles Enhance Platelet-Derived Growth Factor-Induced Chemokine Expression by Mesothelial Cells via Prolonged Mitogen-Activated Protein Kinase Activation}, volume={47}, ISSN={["1535-4989"]}, DOI={10.1165/rcmb.2012-0023oc}, abstractNote={Pleural diseases (fibrosis and mesothelioma) are a major concern for individuals exposed by inhalation to certain types of particles, metals, and fibers. Increasing attention has focused on the possibility that certain types of engineered nanoparticles (NPs), especially those containing nickel, might also pose a risk for pleural diseases. Platelet-derived growth factor (PDGF) is an important mediator of fibrosis and cancer that has been implicated in the pathogenesis of pleural diseases. In this study, we discovered that PDGF synergistically enhanced nickel NP (NiNP)-induced increases in mRNA and protein levels of the profibrogenic chemokine monocyte chemoattractant protein-1 (MCP-1 or CCL2), and the antifibrogenic IFN-inducible CXC chemokine (CXCL10) in normal rat pleural mesothelial 2 (NRM2) cells in vitro. Carbon black NPs (CBNPs), used as a negative control NP, did not cause a significant increase in CCL2 or CXCL10 in the absence or presence of PDGF. NiNPs prolonged PDGF-induced phosphorylation of the mitogen-activated protein kinase family termed extracellular signal-regulated kinases (ERK)-1 and -2 for up to 24 hours, and NiNPs also synergistically increased PDGF-induced hypoxia-inducible factor (HIF)-1α protein levels in NRM2 cells. Inhibition of ERK-1,2 phosphorylation with the mitogen-activated protein kinase kinase (MEK) inhibitor, PD98059, blocked the synergistic increase in CCL2, CXCL10, and HIF-1α levels induced by PDGF and NiNPs. Moreover, the antioxidant, N-acetyl-L-cysteine (NAC), significantly reduced HIF-1α, ERK-1,2 phosphorylation, and CCL2 protein levels that were synergistically increased by the combination of PDGF and NiNPs. These data indicate that NiNPs enhance the activity of PDGF in regulating chemokine production in NRM2 cells through a mechanism involving reactive oxygen species generation and prolonged activation of ERK-1,2.}, number={4}, journal={AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY}, author={Glista-Baker, Ellen E. and Taylor, Alexia J. and Sayers, Brian C. and Thompson, Elizabeth A. and Bonner, James C.}, year={2012}, month={Oct}, pages={552–561} }
 @article{cesta_ryman-rasmussen_wallace_masinde_hurlburt_taylor_bonner_2010, title={Bacterial Lipopolysaccharide Enhances PDGF Signaling and Pulmonary Fibrosis in Rats Exposed to Carbon Nanotubes}, volume={43}, ISSN={["1535-4989"]}, DOI={10.1165/rcmb.2009-0113oc}, abstractNote={Engineered multi-walled carbon nanotubes (MWCNT) represent a possible health risk for pulmonary fibrosis due to their fiber-like shape and potential for persistence in the lung. We postulated that bacterial lipopolysaccharide (LPS), a ubiquitous agent in the environment that causes lung inflammation, would enhance fibrosis caused by MWCNT. Rats were exposed to LPS and then intratracheally instilled with MWCNT or carbon black (CB) nanoparticles 24 hours later. Pulmonary fibrosis was observed 21 days after MWCNT exposure, but not with CB. LPS alone caused no fibrosis but enhanced MWCNT-induced fibrosis. LPS plus CB did not significantly increase fibrosis. MWCNT increased platelet-derived growth factor-AA (PDGF-AA), a major mediator of fibrosis. PDGF-AA production in response to MWCNT, but not CB, was synergistically enhanced by LPS. Immunostaining showed PDGF-AA in bronchiolar epithelial cells and macrophages. Since macrophages engulfed MWCNT, were positive for PDGF-AA, and mediate fibroblast responses, experiments were performed with rat lung macrophages (NR8383 cells) and rat lung fibroblasts in vitro. LPS exposure increased PDGF-A mRNA levels in NR8383 cells and enhanced MWCNT-induced PDGF-A mRNA levels. Moreover, LPS increased MWCNT- or CB-induced PDGF receptor-alpha (PDGF-Ralpha) mRNA in fibroblasts. Our data suggest that LPS exacerbates MWCNT-induced lung fibrosis by amplifying production of PDGF-AA in macrophages and epithelial cells, and by increasing PDGF-Ralpha on pulmonary fibroblasts. Our findings also suggest that individuals with pre-existing pulmonary inflammation are at greater risk for the potential adverse effects of MWCNT.}, number={2}, journal={AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY}, author={Cesta, Mark F. and Ryman-Rasmussen, Jessica P. and Wallace, Duncan G. and Masinde, Tiwanda and Hurlburt, Geoffrey and Taylor, Alexia J. and Bonner, James C.}, year={2010}, month={Aug}, pages={142–151} }