@article{takashi_pettersen_park_fang_akley_adler_2005, title={A peptide directed against the N-terminus of MARCKS protein attenuates release of myeloperoxidase (MPO) from human and canine neutrophils in vitro.}, volume={2}, journal={404nOtfound}, author={Takashi, S. and Pettersen, C. A. and Park, J. and Fang, S. and Akley, N. J. and Adler, K. B.}, year={2005}, pages={A633} }
 @misc{martin_adler_macchione_akley_mckane_2005, title={Culture system for mouse tracheal epithelial cells}, volume={6,933,149}, number={2005 Aug. 23}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Martin, L. D. and Adler, K. B. and Macchione, M. and Akley, N. J. and McKane, S. A.}, year={2005} }
 @article{lankford_macchione_crews_mckane_akley_martin_2005, title={Modeling the airway epithelium in allergic asthma: Interleukin-13-induced effects in differentiated murine tracheal epithelial cells}, volume={41}, number={7}, journal={In Vitro Cellular & Developmental Biology. Animal}, author={Lankford, S. M. and Macchione, M. and Crews, A. L. and McKane, S. A. and Akley, N. J. and Martin, L. D.}, year={2005}, pages={217–224} }
 @article{martin_adler_akley_crews_sharova_2002, title={Secretion-competent mouse tracheal epithelial cell culture from the genetically altered mouse - Pathway analysis via gene array}, volume={121}, DOI={10.1016/S0012-3692(15)35478-7}, abstractNote={The ability to create knockout and transgenic mice with phenotypes mimicking a variety of lung diseases has led to a large body of knowledge detailing the role of various gene products in the development of these diseases. Similarly, the use of well-differentiated human airway epithelial cell cultures has led to an understanding of precise signaling pathways regulating cellular functions such as mucus secretion, adhesion molecule and cytokine expression, and epithelial cell proliferation. The ability to combine these two powerful research approaches lies with creating an in vitro mouse tracheal epithelial (MTE) cell culture system. Here, we report the development of such a primary cell system that maintains morphologic and functional characteristics of the in vivo mouse airway epithelium. Specifically, epithelial cells dissociated from intact mouse tracheas are grown in air/liquid interface culture in defined media with or without serum. Under both conditions, Alcian blue/periodic acid-Schiff–positive mucous cells are observed. In contrast, ciliary development appears to require serum, suggesting that it may be possible to further manipulate this cell culture system to allow precise study of either mucous or ciliated cell development. This cell culture system has been examined to ensure its epithelial nature as indicated by Western blot analyses showing the culture findings to be positive for cytokeratin 5 expression. Using a mouse mucin 5ac-specific antibody to detect secreted protein by enzyme-linked immunosorbent assay, the cultures are found to secrete mucin constitutively and in a stimulated manner in response to known secretagogues (phorbol 12-myristate 13-acetate and 8-Br-cyclic guanosine monophosphate). Although a single trachea yields only 1 cm2 of differentiated culture, our preliminary studies indicate sufficient material can be obtained to perform gene array analyses of control and interleukin-13–exposed MTE cell cultures. Thus, we anticipate use of the MTE cell culture system not only to determine specific signaling pathways important to airway epithelial cell changes during lung disease, but by employing cells from knockout and transgenic mice, we expect to obtain an understanding of how expression of genes controlling these pathways is altered by genetic changes. In this manner, it should be possible to directly interface in vitro experimentation to define precise signaling pathways in airway epithelial cells with in vivo whole animal studies.}, number={3}, journal={Chest}, author={Martin, L. D. and Adler, K. B. and Akley, N. J. and Crews, A. and Sharova, L.}, year={2002}, pages={79S} }
 @article{macchione_akley_adler_martin_2001, title={Differentiation of murine tracheal epithelial cells in vitro.}, volume={163}, journal={American Journal of Respiratory and Critical Care Medicine}, author={Macchione, M. and Akley, N. J. and Adler, K. B. and Martin, L. D.}, year={2001}, pages={A225} }
 @inbook{martin_macchione_bonner_booth_akley_adler_2001, title={Interleukin-13 induced mucous cell hyperplasia in airway epithelium.}, booktitle={Cilia and mucus: from development to respiratory disease.}, author={Martin, L. D. and Macchione, M. and Bonner, J. C. and Booth, B. W. and Akley, N. J. and Adler, K. B.}, year={2001}, pages={253–263} }
 @article{booth_bonner_akley_macchione_adler_martin_2001, title={Interleukin-13, a mediator of subepithelial fibrosis, enhances growth factor production and proliferation in human airway epithelial cells}, volume={120}, ISSN={["0012-3692"]}, DOI={10.1378/chest.120.1_suppl.S15}, abstractNote={Subepithelial fibrosis is a prominent feature of the remodeled asthmatic airway. The cytokine interleukin (IL)-13, implicated as a mediator in the development of asthma, induces a significant degree of subepithelial fibrosis in the lungs of transgenic mice. Since IL-13 has been shown to exert effects on the airway epithelium, including the development of a mucous phenotype, we have begun to determine whether IL-13 provokes production of factors from the epithelium that could elicit the observed subepithelial fibrotic response. In the studies reported herein, injured airways with regions of regenerating/differentiating cells and regions of normal fully differentiated cells have been mimicked by examining the effects of IL-13 on normal human bronchial epithelial cells during mucociliary differentiation in air/liquid interface culture. Exposure of normal human bronchial epithelial cells to IL-13 resulted in increased production of soluble transforming growth factor (TGF)-a, with the growth factor interacting in an autocrine manner with the epidermal growth factor receptor. Production of soluble TGF-a was very rapid, with a threefold increase observed in response to IL-13 (10 ng/mL) b y1ho fexposure. Continuous exposure to IL-13 throughout the course of mucociliary differentiation (a total of 10 days) resulted in a twofold increase in cell number by day 7 when cells are differentiated. Exposure to IL-13 (10 ng/mL; 24 h) provoked a threefold increase in proliferation once the cells were differentiated, an effect that could be duplicated in differ}, number={1}, journal={CHEST}, author={Booth, B and Bonner, J and Akley, N and Macchione, M and Adler, K and Martin, LD}, year={2001}, month={Jul}, pages={15S–15S} }
 @inbook{he_adler_akley_fischer_jiang_krunkosky_martin_2000, title={Air-liquid interface culture systems for exposure of differentiated cells to oxidant stress.}, booktitle={Models and methods in cell signaling and gene expression applications to oxidative stress research.}, author={He, F. and Adler, K. B. and Akley, N. J. and Fischer, B. M. and Jiang, N. and Krunkosky, T. M. and Martin, L. D.}, year={2000}, pages={15–30} }
 @article{krunkosky_fischer_martin_jones_akley_adler_2000, title={Effects of TNF-alpha on expression of ICAM-1 in human airway epithelial cells in vitro - Signaling pathways controlling surface and gene expression}, volume={22}, ISSN={["1535-4989"]}, DOI={10.1165/ajrcmb.22.6.3925}, abstractNote={Signaling pathways associated with tumor necrosis factor (TNF)- α –induced intercellular adhesion molecule 1 (ICAM-1) surface and gene expression were investigated in well differentiated normal human bronchial epithelial (NHBE) cells in air–liquid interface primary culture. Cells were exposed to human recombinant TNF- α (hrTNF- α ; 0.015 to 150 ng/ml [specific activity, 2.86 × 107 U/mg]). TNF- α enhanced ICAM-1 surface expression (measured by flow cytometry) and steady-state messenger RNA (mRNA) levels (assessed by Northern hybridization) in concentration- and time-dependent manners. TNF- α –induced ICAM-1 surface and gene expression were both blocked by the RNA polymerase II inhibitor actinomycin D (0.1 μ g/ml), and surface expression was attenuated by a neutralizing monoclonal antibody directed against the TNF- α receptor p55 (TNF-RI). The intracellular signaling pathway leading to enhanced expression appeared to involve activation of a phospholipase C that hydrolyzes phosphatidylcholine (PC-PLC) becaus...}, number={6}, journal={AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY}, author={Krunkosky, TM and Fischer, BM and Martin, LD and Jones, N and Akley, NJ and Adler, KB}, year={2000}, month={Jun}, pages={685–692} }
 @article{martin_bonner_macchione_booth_akley_adler_2000, title={Interaction of TGF? and EGF receptor mediates IL-13 induced mucous cell hyperplasia in human airway epithelium in vitro.}, volume={161}, journal={American Journal of Respiratory and Critical Care Medicine}, author={Martin, L. D. and Bonner, J. C. and Macchione, M. and Booth, B. and Akley, N. and Adler, K. B.}, year={2000}, pages={A779} }
 @article{fischer_rochelle_voynow_akley_adler_1999, title={Tumor necrosis factor-alpha stimulates mucin secretion and cyclic GMP production by guinea pig tracheal epithelial cells in vitro}, volume={20}, ISSN={["1044-1549"]}, DOI={10.1165/ajrcmb.20.3.3393}, abstractNote={Tumor necrosis factor (TNF)-alpha, a pluripotent cytokine implicated in the pathogenesis of airway inflammation, has been shown to provoke hypersecretion of mucin by airway epithelial cells in vitro. In this study, we investigated potential signaling pathways mediating TNF-alpha-induced mucin secretion using guinea pig tracheal epithelial (GPTE) cells in air-liquid interface culture. Exogenously applied TNF-alpha (human recombinant) stimulated mucin secretion in a concentration-dependent manner, with maximal effects at 10 to 15 ng/ml (286 to 429 U/ml). The pathway of stimulated secretion appeared to involve generation of intracellular nitric oxide (NO), activation of soluble guanylate cyclase (GC-S), production of cyclic guanosine monophosphate (cGMP), and activation of cGMP-dependent protein kinase (PKG). TNF-alpha increased production of nitrite and nitrate by GPTE cells; both mucin secretion and cGMP production were attenuated by NG-monomethyl-L-arginine (1 mM), a competitive inhibitor of nitric oxide synthase (NOS), or by the GC-S inhibitor LY83583 (50 microM); and mucin secretion in response to TNF-alpha or to the cGMP analogue dibutyryl cGMP (100 and 500 microM) was attenuated by the specific PKG inhibitor KT5823 (1 microM). Increased mucin secretion and increased cGMP production in response to TNF-alpha both appeared to be mediated by a phospholipase C that hydrolyzes phosphatidylcholine (PC-PLC), and by protein kinase C (PKC), since both responses were attenuated by either D609 (10 and 20 microg/ml), a specific PC-PLC inhibitor, or by each of three PKC inhibitors: Calphostin C (0.3 and 0.5 microM), bisindoylmaleimide (GF 109203X, Go 6850; 20 nM), or Ro31-8220 (10 microM). Collectively, the results suggest that TNF-alpha stimulates secretion of mucin by GPTE cells via a mechanism(s) dependent on PC-PLC and PKC, and involving activation of NOS, generation of NO, production of cGMP, and activation of PKG.}, number={3}, journal={AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY}, author={Fischer, BM and Rochelle, LG and Voynow, JA and Akley, NJ and Adler, KB}, year={1999}, month={Mar}, pages={413–422} }
 @article{rochelle_fischer_boehm_akley_adler_1997, title={Inflammatory mediators increase intracellular reactive oxygen and nitrogen species (ROS/RNS) in airway epithelial cells.}, volume={155}, journal={American Journal of Respiratory and Critical Care Medicine}, author={Rochelle, L. G. and Fischer, B. M. and Boehm, K. A. and Akley, N. J. and Adler, K. B.}, year={1997}, pages={A437} }
 @article{murphy_akley_chitapo_adler_1997, title={Secretory inhibition by airway epithelium increases with age.}, volume={155}, journal={American Journal of Respiratory and Critical Care Medicine}, author={Murphy, T. M. and Akley, N. J. and Chitapo, P. and Adler, K.}, year={1997}, pages={A427} }
 @article{martin_krunkosky_dye_fischer_jiang_rochelle_akley_dreher_adler_1997, title={The role of reactive oxygen and nitrogen species in the response of airway epithelium to particulates}, volume={105}, ISSN={["1552-9924"]}, DOI={10.2307/3433551}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Martin, LD and Krunkosky, TM and Dye, JA and Fischer, BM and Jiang, NF and Rochelle, LG and Akley, NJ and Dreher, KL and Adler, KB}, year={1997}, month={Sep}, pages={1301–1307} }
 @article{wright_fischer_li_rochelle_akley_adler_1996, title={Oxidant stress stimulates mucin secretion and PLG in airway epithelium via a nitric oxide-dependent mechanism}, volume={271}, ISSN={["1040-0605"]}, DOI={10.1152/ajplung.1996.271.5.l854}, abstractNote={ Reactive oxygen species (ROS) have been implicated in the pathogenesis of a wide variety of respiratory diseases. We investigated mechanisms of ROS-induced mucin secretion by guinea pig tracheal epithelial (GPTE) cells in primary culture, and ROS-induced activation of the second messenger-producing enzyme phospholipase C (PLC), in GPTE cells and in a virally transformed cell line (BEAS-2B) derived from human bronchial epithelium. Mucin secretion was measured by a monoclonal antibody-based enzyme-linked immunosorbent assay, and PLC activation was assessed by anion exchange chromatography. ROS generated enzymatically by xanthine oxidase (XO, 500 microM) in the presence of purine (500 microM) enhanced release of mucin by GPTE cells and activated PLC in GPTE and BEAS cells. Hypersecretion of mucin and activation of PLC in response to purine + XO appeared to occur via an intracellular pathway(s) dependent on endogenously produced nitric oxide and possibly intracellularly generated oxidants. Both responses could be blocked or attenuated by preincubation of the cells with NG-monomethyl-L-arginine, an inhibitor of the enzyme nitric oxide synthase, or with dimethylthiourea, a compound that can react with a variety of intracellular oxidant species. Reactive nitrogen species generated chemically also stimulated secretion of mucin and activated PLC via a mechanism dependent (at least in part) on intracellular oxidant-mediated process(es). The results suggest that intracellularly generated radical species of nitrogen and oxygen may be important modulators of the response of airway epithelial cells to external oxidant stress. }, number={5}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY}, author={Wright, DT and Fischer, BM and Li, CM and Rochelle, LG and Akley, NJ and Adler, KB}, year={1996}, month={Nov}, pages={L854–L861} }
 @article{krunkosky_fischer_akley_adler_1996, title={Tumor necrosis factor alpha (TNF alpha)-induced ICAM-1 surface expression in airway epithelial cells in vitro: Possible signal transduction mechanisms}, volume={796}, ISBN={["0-89766-979-7"]}, ISSN={["0077-8923"]}, DOI={10.1111/j.1749-6632.1996.tb32564.x}, abstractNote={Within the past several years research on the interaction of cytokines and adhesion molecules with airway epithelium in diseases has allowed us to develop a better understanding of the disease process. The cytokine, TNF alpha and the adhesion molecule ICAM-1 are important mediators in the pathogenesis of airway diseases such as asthma, chronic bronchitis, and adult respiratory distress syndrome. Effects of TNF alpha on ICAM-1 surface expression was investigated in both primary cultures of normal human bronchial epithelial (NHBE) cells and immortalized human bronchial epithelial cell line BEAS-2B. TNF alpha (0.015-150 ng/mL) significantly enhanced ICAM-1 surface expression (measured by flow cytometry) in a dose and time-dependent manner, with peak expression seen at 24 hours. This response was negated by heat inactivation of the TNF alpha prior to incubation. TNF alpha-induced ICAM-1 expression also was inhibited by pre- and coincubation of TNF alpha with 3 micrograms/mL soluble TNF-R1 or by the PKC inhibitor, Calphostin C (0.1 and 0.5 microM). The ROI scavengers, dimethylthiourea (4 mM), and dimethyl sulfoxide (0.001%), enhanced TNF alpha-induced ICAM-1 expression. Collectively, these results indicate that TNF alpha-induced ICAM-1 surface expression is a specific receptor-mediated response (TNF-R1), which is mediated by mechanisms dependent on PKC and intracellular reactive oxygen species.}, journal={CYTOKINES AND ADHESION MOLECULES IN LUNG INFLAMMATION}, author={Krunkosky, TM and Fischer, BM and Akley, NJ and Adler, KB}, year={1996}, pages={30–37} }
 @article{fischer_rochelle_akley_adler_1996, title={Tumor necrosis factor-alpha (TNF?) induced mucin secretion: dependence on nitric oxide (NO) and cyclic GMP.}, volume={153}, journal={American Journal of Respiratory and Critical Care Medicine}, author={Fischer, B. M. and Rochelle, L. G. and Akley, N. J. and Adler, K. B.}, year={1996}, pages={A538} }
 @article{krunkosky_fischer_wright_akley_adler_1995, title={Effects of tumor necrosis factor alpha (TNF?) on expression of ICAM-1 and inflammation-associated genes in airway epithelial cells in vitro.}, volume={151}, journal={American Journal of Respiratory and Critical Care Medicine}, author={Krunkosky, T. M. and Fischer, B. M. and Wright, D. T. and Akley, N. J. and Adler, K. B.}, year={1995}, pages={A366} }
 @article{fischer_wright_li_li_cohn_akley_adler_1995, title={Endogenously-generated nitric oxide (NO) may be a key signaling molecule in hypersecretion of mucin by guinea pig tracheal epithelial (GPTE) cells in vitro.}, volume={151}, journal={American Journal of Respiratory and Critical Care Medicine}, author={Fischer, B. M. and Wright, D. T. and Li, H. and Li, C. M. and Cohn, L. A. and Akley, N. J. and Adler, K. B.}, year={1995}, pages={A337} }
 @article{wright_li_fischer_akley_adler_1995, title={Reactive nitrogen species (RNS) stimulate secretion of mucin by primary cultures of guinea pig tracheal epithelial (GPTE) cells.}, volume={151}, journal={American Journal of Respiratory and Critical Care Medicine}, author={Wright, D. T. and Li, C. M. and Fischer, B. M. and Akley, N. J. and Adler, K. B.}, year={1995}, pages={A337} }
 @article{adler_wright_fischer_cohn_li_li_choe_akley_1994, title={Effects of oxidant stress on airway epithelial cells in vitro.}, volume={8}, journal={FASEB Journal}, author={Adler, K. B. and Wright, D. T. and Fischer, B. M. and Cohn, L. A. and Li, C. and Li, H. and Choe, N. H. and Akley, N. J.}, year={1994}, pages={A896} }
 @article{wright_akley_li_fischer_adler_1994, title={Reactive oxygen species (ROS) activate phospholipase C in guinea pig and human airway epithelial cells in vitro.}, volume={149}, journal={American Journal of Respiratory and Critical Care Medicine}, author={Wright, D. T. and Akley, N. J. and Li, H. and Fischer, B. M. and Adler, K. B.}, year={1994}, pages={A315} }
 @article{adler_fischer_akley_dolan-o'keefe_1994, title={Tumor necrosis factor alpha (TNF?) stimulates mucin secretion and gene expression in airway epithelium in vitro.}, volume={37}, journal={Proceedings of the 37th Aspen Lung Conference.}, author={Adler, K. B. and Fischer, B. M. and Akley, N. J. and Dolan-O'Keefe, M.}, year={1994}, pages={17} }
 @article{friedman_wright_dailey_akley_devlin_adler_1992, title={Ozone increases platelet activating factor and activates phospholipases (PLA2 and PLC) in primary guinea pig tracheal epithelial cells (GPTE).}, volume={145}, journal={American Review of Respiratory Disease}, author={Friedman, M. and Wright, D. T. and Dailey, L. A. and Akley, N. J. and Devlin, R. B. and Adler, K. B.}, year={1992}, pages={A99} }
 @article{adler_kinnula_akley_crapo_1991, title={Airway epithelium generates and releases reactive oxygen species in response to activation of protein kinase C.}, volume={4}, journal={Proceedings fo the 4th International Conference on Environmental Lung Disease (Montreal, 1991)}, author={Adler, K. B. and Kinnula, V. and Akley, N. J. and Crapo, J. D.}, year={1991}, pages={2} }
 @article{adler_kinnula_akley_lee_crapo_1991, title={Effects of inflammatory mediators on generation and release of reactive oxygen species by airway epithelium in vitro.}, volume={34}, journal={Proceedings of the 34th Aspen Lung Conference.}, author={Adler, K. B. and Kinnula, V. and Akley, N. J. and Lee, J. and Crapo, J. D.}, year={1991}, pages={33} }
 @inbook{lee_akley_adler_1991, title={Methods to study interactions between inhaled substances and epithelium of the respiratory tract in vitro.}, booktitle={Microbeam analysis- 1990.}, author={Lee, J. and Akley, N. J. and Adler, K. B.}, year={1991}, pages={457–458} }
 @article{glasgow_akley_adler_1991, title={Platelet activating factor provokes release of mucin like glycoproteins from guinea pig tracheal epithelial cells via a lipoxygenase-dependent mechanism.}, volume={143}, journal={American Review of Respiratory Disease}, author={Glasgow, W. and Akley, N. J. and Adler, K. B.}, year={1991}, pages={A147} }
 @article{adler_akley_lee_1990, title={Oxygen metabolites stimulate inositol lipid turnover in guinea pig airway epithelial cells in organotypic culture.}, volume={141}, journal={American Review of Respiratory Disease}, author={Adler, K. B. and Akley, N. J. and Lee, J.}, year={1990}, pages={A107} }
 @inbook{adler_akley_ayers_holden-stauffer_khosla_kim_1989, title={A novel culture system for maintaining differentiated epithelial cells between air and liquid phases: A possible model for studying interactions between mineral fibers, gases and airway epithelium.}, booktitle={Biological interaction of inhaled mineral fibers and cigarette smoke}, author={Adler, K. B. and Akley, N. J. and Ayers, G. and Holden-Stauffer, W. J. and Khosla, J. B. and Kim, K. C.}, year={1989}, pages={381–390} }
 @article{adler_akley_holden-stauffer_1989, title={Oxidant injury to rodent airway epithelium in primary culture stimulates intracellular production of oxygen free radicals, arachidonic acid metabolism, and mucin secretion.}, volume={139}, journal={American Review of Respiratory Disease}, author={Adler, K. B. and Akley, N. J. and Holden-Stauffer, W. J.}, year={1989}, pages={A403} }
 @article{adler_akley_holden-stauffer_1988, title={Oxidant injury to airway epithelium in vitro stimulates cyclooxygenase metabolism of arachidonic acid and secretion of mucin.}, volume={107}, journal={Journal of Cell Biology}, author={Adler, K. B. and Akley, N. J. and Holden-Stauffer, W. J.}, year={1988}, pages={350a} }
 @inbook{adler_akley_1988, title={Oxygen radicals stimulate secretion of mucin by rodent airway epithelial cells in organotypic culture.}, booktitle={Oxy radicals in molecular biology and pathology}, author={Adler, K. B. and Akley, N. J.}, year={1988}, pages={101–108} }