@article{nighot_young_nighot_rawat_sung_maharshak_plevy_ma_blikslager_2013, title={Chloride Channel ClC-2 is a Key Factor in the Development of DSS-induced Murine Colitis}, volume={19}, ISSN={1078-0998}, url={http://dx.doi.org/10.1097/MIB.0b013e3182a82ae9}, DOI={10.1097/mib.0b013e3182a82ae9}, abstractNote={Background:Previously, it was shown that the chloride channel ClC-2 modulates intestinal tight junction (TJ) barrier function. The aim of the present study was to investigate the role of ClC-2 in epithelial barrier function and recovery in the event of epithelial injury. Methods:The role of ClC-2 was investigated in TJ barrier function in dextran sodium sulfate (DSS)-induced colitis in ClC-2 knockout mice and ClC-2 knockdown intestinal Caco-2 cells. Barrier function was measured electrophysiologically and by transepithelial mannitol fluxes. Selected TJ and associated proteins were Western blotted, cytokines were measured using quantitative PCR, and human colonic biopsies were examined with immunohistochemistry. Results:ClC-2−/− mice had a higher disease activity index, higher histological scores, and increased paracellular permeability compared with wild-type mice when treated with DSS. DSS-treated ClC-2−/− mice had increased claudin-2 expression, greater loss of occludin in the membrane, increased association of occludin with caveolin-1, and significantly increased tumor necrosis factor-&agr; and interleukin-1&bgr; messenger RNA. ClC-2 knockdown in human intestinal Caco-2 cells resulted in a greater loss of epithelial resistance in the event of epithelial injury. The restoration of colonic barrier function after DSS colitis was delayed in ClC-2−/− mice. In human colonic biopsies, the protein and messenger RNA expression of ClC-2 was found to be reduced in patients with ulcerative colitis. Conclusions:ClC-2 plays a critical role in experimental colitis in that its absence increases disease activity, reduces barrier function and recovery, and perturbs TJs. Furthermore, ClC-2 expression is markedly reduced in the colon of human patients with ulcerative colitis.}, number={13}, journal={Inflammatory Bowel Diseases}, publisher={Oxford University Press (OUP)}, author={Nighot, Prashant and Young, Karen and Nighot, Meghali and Rawat, Manmeet and Sung, Eui J. and Maharshak, Nitsan and Plevy, Scott E. and Ma, Thomas and Blikslager, Anthony}, year={2013}, month={Dec}, pages={2867–2877} }
 @article{little_white_young_blikslager_2005, title={Faecal bile loss in horses following small intestinal resection}, volume={37}, ISSN={["0425-1644"]}, DOI={10.2746/0425164054406883}, abstractNote={Equine Veterinary JournalVolume 37, Issue 1 p. 92-94 Faecal bile loss in horses following small intestinal resection D. LITTLE, D. LITTLE Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this authorC. E. WHITE, C. E. WHITE Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this authorK. M. YOUNG, K. M. YOUNG Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this authorA. T. BLIKSLAGER, Corresponding Author A. T. BLIKSLAGER Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USADepartment of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this author D. LITTLE, D. LITTLE Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this authorC. E. WHITE, C. E. WHITE Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this authorK. M. YOUNG, K. M. YOUNG Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this authorA. T. BLIKSLAGER, Corresponding Author A. T. BLIKSLAGER Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USADepartment of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this author First published: 05 January 2010 https://doi.org/10.2746/0425164054406883Citations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume37, Issue1January 2005Pages 92-94 RelatedInformation}, number={1}, journal={EQUINE VETERINARY JOURNAL}, author={Little, D and White, CE and Young, KM and Blikslager, AT}, year={2005}, month={Jan}, pages={92–94} }
 @article{tomlinson_wilder_young_blikslager_2004, title={Effects of flunixin meglumine or etodolac treatment on mucosal recovery of equine jejunum after ischemia}, volume={65}, ISSN={["1943-5681"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-3042571674&partnerID=MN8TOARS}, DOI={10.2460/ajvr.2004.65.761}, abstractNote={Abstract}, number={6}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Tomlinson, JE and Wilder, BO and Young, KM and Blikslager, AT}, year={2004}, month={Jun}, pages={761–769} }
 @article{shifflett_bottone_young_moeser_jones_blikslager_2004, title={Neutrophils augment recovery of porcine ischemia-injured ileal mucosa by an IL-1β- and COX-2-dependent mechanism}, volume={287}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00076.2003}, DOI={10.1152/ajpgi.00076.2003}, abstractNote={Polymorphonuclear neutrophils (PMNs) play a critical role in intestinal mucosal injury and repair. To study effects of PMNs on acutely injured mucosa, we applied PMNs isolated from circulation or peritoneal fluid from animals with chemically induced peritonitis to ischemia-injured porcine ileal mucosa. In preliminary experiments, PMNs enhanced recovery of transepithelial electrical resistance (TER), and this action was inhibited by pretreatment with the nonselective cyclooxygenase (COX) inhibitor indomethacin. Because COX-2 is upregulated by inflammatory mediators such as IL-1β, which is released by PMNs, we postulated that PMNs enhance recovery of ischemia-injured mucosa by a pathway involving IL-1β and COX-2. Application of 5 × 106PMNs to the serosal surface of ischemia-injured mucosa significantly enhanced recovery of TER ( P < 0.05), an effect that was inhibited by the selective COX-2 inhibitor NS-398 (5 μM) and by an IL-1β receptor antagonist (0.1 mg/ml). Addition of 10 ng/ml IL-1β to the serosal surface of injured tissues caused a significant increase in TER ( P < 0.05) that was inhibited by pretreatment with NS-398. Western blot analysis of mucosal homogenates revealed dramatic upregulation of COX-2 in response to IL-1β or peritoneal PMNs, and the latter was inhibited by an IL-1β receptor antagonist. Real-time PCR revealed that increased mRNA COX-2 expression preceded increased COX-2 protein expression in response to IL-1β. We concluded that PMNs augment recovery of TER in ischemia-injured ileal mucosa via IL-1β-dependent upregulation of COX-2.}, number={1}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Shifflett, Donnie E. and Bottone, Frank G., Jr. and Young, Karen M. and Moeser, Adam J. and Jones, Samuel L. and Blikslager, Anthony T.}, year={2004}, month={Jul}, pages={G50–G57} }
 @article{little_dean_young_mckane_martin_jones_blikslager_2003, title={PI3K signaling is required for prostaglandin-induced  mucosal recovery in ischemia-injured porcine ileum}, volume={284}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00121.2002}, DOI={10.1152/ajpgi.00121.2002}, abstractNote={ We have previously shown that PGE2 and PGI2 induce recovery of transepithelial resistance (TER) in ischemia-injured porcine ileal mucosa, associated with initial increases in Cl−secretion. We believe that the latter generates an osmotic gradient that stimulates resealing of tight junctions. Because of evidence implicating phosphatidylinositol 3-kinase (PI3K) in regulating tight junction assembly, we postulated that this signaling pathway is involved in PG-induced mucosal recovery. Porcine ileum was subjected to 45 min of ischemia, after which TER was monitored for a 180-min recovery period. Endogenous PG production was inhibited with indomethacin (5 μM). PGE2 (1 μM) and PGI2(1 μM) stimulated recovery of TER, which was inhibited by serosal application of the osmotic agent urea (300 mosmol/kgH2O). The PI3K inhibitor wortmannin (10 nM) blocked recovery of TER in response to PGs or mucosal urea. Immunofluorescence imaging of recovering epithelium revealed that PGs restored occludin and zonula occludens-1 distribution to interepithelial junctions, and this pattern was disrupted by pretreatment with wortmannin. These experiments suggest that PGs stimulate recovery of paracellular resistance via a mechanism involving transepithelial osmotic gradients and PI3K-dependent restoration of tight junction protein distribution. }, number={1}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Little, Dianne and Dean, Rebecca A. and Young, Karen M. and McKane, Shaun A. and Martin, Linda D. and Jones, Samuel L. and Blikslager, Anthony T.}, year={2003}, month={Jan}, pages={G46–G56} }
 @article{blikslager_zimmel_young_campbell_little_argenzio_2002, title={Recovery of ischaemic injured porcine ileum: evidence for a contributory role of COX-1 and COX-2}, volume={50}, ISSN={0017-5749}, url={http://dx.doi.org/10.1136/gut.50.5.615}, DOI={10.1136/gut.50.5.615}, abstractNote={Background: We have previously shown that the non-selective cyclooxygenase (COX) inhibitor indomethacin retards recovery of intestinal barrier function in ischaemic injured porcine ileum. However, the relative role of COX-1 and COX-2 elaborated prostaglandins in this process is unclear. Aims: To assess the role of COX-1 and COX-2 elaborated prostaglandins in the recovery of intestinal barrier function by evaluating the effects of selective COX-1 and COX-2 inhibitors on mucosal recovery and eicosanoid production. Methods: Porcine ileal mucosa subjected to 45 minutes of ischaemia was mounted in Ussing chambers, and transepithelial electrical resistance was used as an indicator of mucosal recovery. Prostaglandins E1 and E2 (PGE) and 6-keto-PGF1α (the stable metabolite of prostaglandin I2 (PGI2)) were measured using ELISA. Thromboxane B2 (TXB2, the stable metabolite of TXA2) was measured as a likely indicator of COX-1 activity. Results: Ischaemic injured tissues recovered to control levels of resistance within three hours whereas tissues treated with indomethacin (5×10−6 M) failed to fully recover, associated with inhibition of eicosanoid production. Injured tissues treated with the selective COX-1 inhibitor SC-560 (5×10−6 M) or the COX-2 inhibitor NS-398 (5×10−6 M) recovered to control levels of resistance within three hours, associated with significant elevations of PGE and 6-keto-PGF1α compared with untreated tissues. However, SC-560 significantly inhibited TXB2 production whereas NS-398 had no effect on this eicosanoid, indicating differential actions of these inhibitors related to their COX selectivity. Conclusions: The results suggest that recovery of resistance is triggered by PGE and PGI2, which may be elaborated by either COX-1 or COX-2.}, number={5}, journal={Gut}, publisher={BMJ}, author={Blikslager, A.T. and Zimmel, D.N. and Young, K.M. and Campbell, N.B. and Little, D. and Argenzio, R.A.}, year={2002}, month={May}, pages={615–623} }
 @article{blikslager_pell_young_2001, title={PGE2 triggers recovery of transmucosal resistance via EP receptor cross talk in porcine ischemia-injured ileum}, volume={281}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.2001.281.2.G375}, DOI={10.1152/ajpgi.2001.281.2.g375}, abstractNote={16,16-Dimethyl-PGE2(PGE2) may interact with one of four prostaglandin type E (EP) receptors, which signal via cAMP (via EP2or EP4receptors) or intracellular Ca2+(via EP1receptors). Furthermore, EP3receptors have several splice variants, which may signal via cAMP or intracellular Ca2+. We sought to determine the PGE2receptor interactions that mediate recovery of transmucosal resistance ( R) in ischemia-injured porcine ileum. Porcine ileum was subjected to 45 min of ischemia, after which the mucosa was mounted in Ussing chambers. Tissues were pretreated with indomethacin (5 μM). Treatment with the EP1, EP2, EP3, and EP4agonist PGE2(1 μM) elevated R twofold and significantly increased tissue cAMP content, whereas the EP2and EP4agonist deoxy-PGE1(1 μM) or the EP1and EP3agonist sulprostone (1 μM) had no effect. However, a combination of deoxy-PGE1and sulprostone stimulated synergistic elevations in R and tissue cAMP content. Furthermore, treatment of tissues with deoxy-PGE1and the Ca2+ionophore A-23187 stimulated synergistic increases in R and cAMP, indicating that PGE2triggers recovery of R via EP receptor cross talk mechanisms involving cAMP and intracellular Ca2+.}, number={2}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Blikslager, Anthony T. and Pell, Susan M. and Young, Karen M.}, year={2001}, month={Aug}, pages={G375–G381} }
 @article{blikslager_roberts_young_rhoads_argenzio_2000, title={Genistein augments prostaglandin-induced recovery  of barrier function in ischemia-injured porcine ileum}, volume={278}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.2000.278.2.G207}, DOI={10.1152/ajpgi.2000.278.2.g207}, abstractNote={We have previously shown that PGE2enhances recovery of transmucosal resistance ( R) in ischemia-injured porcine ileum via a mechanism involving chloride secretion. Because the tyrosine kinase inhibitor genistein amplifies cAMP-induced Cl−secretion, we postulated that genistein would augment PGE2-induced recovery of R. Porcine ileum subjected to 45 min of ischemia was mounted in Ussing chambers, and R and mucosal-to-serosal fluxes of [3H] N-formyl-methionyl-leucyl phenylalanine (FMLP) and [3H]mannitol were monitored as indicators of recovery of barrier function. Treatment with genistein (10−4M) and PGE2(10−6M) resulted in synergistic elevations in R and additive reductions in mucosal-to-serosal fluxes of [3H]FMLP and [3H]mannitol, whereas treatment with genistein alone had no effect. Treatment of injured tissues with genistein and either 8-bromo-cAMP (10−4M) or cGMP (10−4M) resulted in synergistic increases in R. However, treatment of tissues with genistein and the protein kinase C (PKC) agonist phorbol myristate acetate (10−5–10−6M) had no effect on R. Genistein augments recovery of Rin the presence of cAMP or cGMP but not in the presence of PKC agonists.}, number={2}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Blikslager, Anthony T. and Roberts, Malcolm C. and Young, Karen M. and Rhoads, J. Marc and Argenzio, Robert A.}, year={2000}, month={Feb}, pages={G207–G216} }