Expression of cyclooxygenase-1 and -2 in the left dorsal colon after different durations of ischemia and reperfusion in horses

Alison J. Morton Island Whirl Equine Colic Research Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.

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Astrid Grosche Island Whirl Equine Colic Research Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.

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Anna K. Rötting Equine Clinic, University of Veterinary Medicine, Bischofsholer Damm 15, 30173 Hannover, Germany.

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Sarah A. Matyjaszek Island Whirl Equine Colic Research Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.

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Anthony T. Blikslager Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

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David E. Freeman Island Whirl Equine Colic Research Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.

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Abstract

Objective—To identify expression and localization of cyclooxygenase (COX)-1 and COX-2 in healthy and ischemic-injured left dorsal colon of horses.

Sample Population—Left dorsal colon tissue samples from 40 horses.

Procedures—Tissue samples that were used in several related studies on ischemia and reperfusion were evaluated. Samples were collected during anesthesia, before induction of ischemia, and following 1 hour of ischemia, 1 hour of ischemia and 30 minutes of reperfusion, 2 hours of ischemia, 2 hours of ischemia and 30 minutes of reperfusion, and 2 hours of ischemia and 18 hours of reperfusion. Histomorphometric analyses were performed to characterize morphological injury. Immunohistochemical analyses were performed to characterize expression and localization of COX-1 and COX-2.

Results—COX-1 and COX-2 were expressed in control tissues before ischemia was induced, predominantly in cells in the lamina propria. Ischemic injury significantly increased expression of COX-2 in epithelial cells on the colonic surface and in crypts. A similar significant increase of COX-1 expression was seen in the epithelial cells.

Conclusions and Clinical Relevance—On the basis of information on the role of COX-2, upregulation of COX-2 in surface epithelium and crypt cells following ischemic injury in equine colon may represent an early step in the repair process.

Abstract

Objective—To identify expression and localization of cyclooxygenase (COX)-1 and COX-2 in healthy and ischemic-injured left dorsal colon of horses.

Sample Population—Left dorsal colon tissue samples from 40 horses.

Procedures—Tissue samples that were used in several related studies on ischemia and reperfusion were evaluated. Samples were collected during anesthesia, before induction of ischemia, and following 1 hour of ischemia, 1 hour of ischemia and 30 minutes of reperfusion, 2 hours of ischemia, 2 hours of ischemia and 30 minutes of reperfusion, and 2 hours of ischemia and 18 hours of reperfusion. Histomorphometric analyses were performed to characterize morphological injury. Immunohistochemical analyses were performed to characterize expression and localization of COX-1 and COX-2.

Results—COX-1 and COX-2 were expressed in control tissues before ischemia was induced, predominantly in cells in the lamina propria. Ischemic injury significantly increased expression of COX-2 in epithelial cells on the colonic surface and in crypts. A similar significant increase of COX-1 expression was seen in the epithelial cells.

Conclusions and Clinical Relevance—On the basis of information on the role of COX-2, upregulation of COX-2 in surface epithelium and crypt cells following ischemic injury in equine colon may represent an early step in the repair process.

Contributor Notes

Supported in part by the American College of Veterinary Surgeons, American Quarter Horse Association, Florida Pari-mutuel Wagering Trust Fund, and University of Florida College of Veterinary Medicine.

Presented at the 9th International Equine Colic Research Symposium, Liverpool, England, June 2008.

Address correspondence to Dr. Morton (mortona@mail.vetmed.ufl.edu).
  • 1.

    Embertson RM, Cook G, Hance SR, et al. Large colon volvulus: surgical treatment of 204 horses (1986–1995), in Proceedings. 42nd Annu Meet Am Assoc Equine Pract 1996;254255.

    • Search Google Scholar
    • Export Citation
  • 2.

    Harrison IW. Equine large intestinal volvulus. A review of 124 cases. Vet Surg 1988;17:7781.

  • 3.

    White N. Epidemiology and etiology of colic. In: The equine acute abdomen. Philadelphia: Lea & Febiger, 1990;56.

  • 4.

    Hughes FE, Slone DE. A modified technique for extensive large colon resection and anastomosis in horses. Vet Surg 1998;27:127131.

  • 5.

    Snyder JR. The pathophysiology of intestinal damage: effects of luminal distension and ischemia. Vet Clin North Am Equine Pract 1989;5:247270.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Argenzio RA, Henrikson CK, Liacos JA. Restitution of barrier and transport function of porcine colon after acute mucosal injury. Am J Physiol 1988;255:G62G71.

    • Search Google Scholar
    • Export Citation
  • 7.

    Blikslager AT, Roberts MC, Rhoads JM, et al. Prostaglandins I2 and E2 have a synergistic role in rescuing epithelial barrier function in porcine ileum. J Clin Invest 1997;100:19281933.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Blikslager AT, Roberts MC, Argenzio RA. Prostaglandin-induced recovery of barrier function in porcine ileum is triggered by chloride secretion. Am J Physiol 1999;276:G28G36.

    • Search Google Scholar
    • Export Citation
  • 9.

    Gookin JL, Galanko JA, Blikslager AT, et al. Prostaglandin-mediated closure of paracellular pathway and not restitution is the primary determinant of barrier recovery in acutely injured porcine ileum. Am J Physiol Gastrointest Liver Physiol 2003;285:G967G979.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Campbell NB, Blikslager AT. The role of cyclooxygenase inhibitors in the repair of ischemic-injured jejunal mucosa in the horse. Equine Vet J Suppl 2000;(32):5964.

    • Search Google Scholar
    • Export Citation
  • 11.

    Nusrat A, Parkos CA, Liang T, et al. Neutrophil migration across model intestinal epithelia: monolayer disruption and subsequent events in epithelial repair. Gastroenterology 1997;113:14891500.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Tomlinson JE, Wilder BO, Young KM, et al. Effects of flunixin meglumine or etodolac treatment on mucosal recovery of equine jejunum after ischemia. Am J Vet Res 2004;65:761769.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Little D, Brown SA, Campbell NB, et al. Effects of the cyclooxygenase inhibitor meloxicam on recovery of ischemia-injured equine jejunum. Am J Vet Res 2007;68:614624.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Rotting AK, Freeman DE, Constable PD, et al. Effects of phenylbutazone, indomethacin, prostaglandin E2, butyrate, and glutamine on restitution of oxidant-injured right dorsal colon of horses in vitro. Am J Vet Res 2004;65:15891595.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Kargman S. Characterization of prostaglandin G/H synthase 1 and 2 in rat, dog, monkey, and human gastrointestinal tracts. Gastroenterology 1996;111:445454.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Warner TD, Mitchell JA. Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic. FASEB J 2004;18:790804.

  • 17.

    Bernardini N, Colucci R, Mattii L, et al. Constitutive expression of cylcoxygenase-2 in the neuromuscular compartment of normal human colon. Neurogastroenterol Motil 2006;18:654662.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Zimmerman KC, Sarbia M, Schror K, et al. Constitutive cyclooxygenase-2 expression in healthy human and rabbit gastric mucosa. Mol Pharmacol 1998;54:536540.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Jackson LM, Wu KC, Mahida YR, et al. Cyclooxygenase (COX) 1 and 2 in normal, inflamed, and ulcerated gastric mucosa. Gut 2000;47:762770.

  • 20.

    Porcher C, Horowitz B, Bayguinov O, et al. Constitutive expression and function of cyclooxygenase-2 in murine gastric muscles. Gastroenterology 2002;122:14421454.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Fornai M, Blandizzi C, Colucci R, et al. Role of cyclooygenases 1 and 2 in the modulation of neuromuscular function in the distal colon of humans and mice. Gut 2005;54:608616.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Porcher C, Horowitz B, Ward SM, et al. Constitutive and functional expression of cyclooxygenase 2 in the murine proximal colon. Neurogastroenterol Motil 2004;16:785799.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Wallace JL, Devchand PR. Emerging roles for cyclooxygenase-2 in gastrointestinal mucosal defense. Br J Pharmacol 2005;145:275282.

  • 24.

    Wallace JL. COX-2: a pivotal enzyme in mucosal protection and resolution of inflammation. ScientificWorldJournal 2006;6:577588.

  • 25.

    Brown SL, Riehl TE, Walker MR, et al. Myd88-dependent positioning of Ptgs2-expressing stromal cells maintains colonic epithelial proliferation during injury. J Clin Invest 2007;117:258269.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Blikslager AT, Zimmel DN, Young KM, et al. Recovery of ischaemic injured porcine ileum: evidence for a contributory role of COX-1 and COX-2. Gut 2002;50:615623.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27.

    Kirtikara K, Morham SG, Raghow R, et al. Compensatory prostaglandin E2 biosynthesis in cyclooxygenase 1 or 2 null cells. J Exp Med 1998;187:517523.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    Matyjaszek SA, Morton AJ, Freeman DE, et al. Effects of flunixin meglumine on recovery of equine colonic mucosa from ischemia. Am J Vet Res 2009;70:236246.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    Pritchett LC, Ulibarri C. Identification of potential physiological and behavioral indicators of postoperative pain in horses after exploratory celiotomy for colic. Appl Anim Behav Sci 2003;80:3143.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30.

    Sellon DC, Roberts MC, Blikslager AT, et al. Effects of continuous rate intravenous infusion on physiologic and outcome variables in horses after celiotomy. J Vet Intern Med 2004;18:555563.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31.

    Rotting AK, Freeman DE, Eurell JA, et al. Effects of acetylcysteine and migration of resident eosinophils in an in vitro model of mucosal injury and restitution in equine right dorsal colon. Am J Vet Res 2003;64:12051212.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32.

    Grosche A, Morton AJ, Polyak MMR, et al. Detection of calprotectin and its correlation to the accumulation of neutrophils within equine large colon during ischemia and reperfusion. Equine Vet J 2008;40:393399.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33.

    Wallace JL, McKnight W, Reuter BK, et al. NSAID-induced gastric damage in rats: requirement for inhibition of both cyclooxygenase 1 and 2. Gastroenterology 2000;119:706714.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34.

    Reuter BK, Asfaha S, Buret A, et al. Exacerbation of inflammation-associated colonic injury in rat through inhibition of cyclooxygenase-2. J Clin Invest 1996;98:20762085.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35.

    Kainulainen H, Rantala I, Collin P, et al. Blisters in the small intestinal mucosa of coeliac patients contain T cells positive for cyclooxygenase 2. Gut 2002;50:8489.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36.

    Wallace JL, Zamuner SR, McKnight W, et al. Aspirin, but not NO-releasing aspirin (NCX-4016), interacts with selective COX-2 inhibitors to aggravate gastric damage and inflammation. Am J Physiol Gastrointest Liver Physiol 2004;286:G76G81.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37.

    Cho WS, Chae C. Expression of cyclooxygenase-2 and nitric oxide synthase 2 in swine ulcerative colitis by Salmonella typhimurium. Vet Pathol 2004;41:419423.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38.

    Moore RM, Bertone AL, Bailey MQ, et al. Neutrophil accumulation in the large colon of horses during low-flow ischemia and reperfusion. Am J Vet Res 1994;55:14541463.

    • Search Google Scholar
    • Export Citation
  • 39.

    Tessner TG, Cohn SM, Schloemann S, et al. PGs prevent decreased epithelial cell proliferation associated with dextran sodium sulfate injury in mice. Gastroenterology 1998;115:874882.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40.

    Wang D, Mann JR, DuBois RN. The role of prostaglandins and other eicosanoids in the gastrointestinal tract. Gastroenterology 2005;128:14451461.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 41.

    Morteau O, Morham SG, Sellon R, et al. Impaired mucosal defense to acute colonic injury in mice lacking cyclooxygenase-1 or cyclooxygenase-2. J Clin Invest 2000;105:469478.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42.

    Tessner TG, Muhale F, Riehl TE, et al. PGE2 reduces radiation-induced epithelial apoptosis through a mechanism involving AKT activation and bax translocation. J Clin Invest 2004;114:16761685.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 43.

    Moore RM, Muir WW, Cawrse M, et al. Systemic and colonic venous plasma eicosanoid and endotoxin concentrations, and colonic venous serum tumor necrosis factor and interleukin-6 activities in horses during low-flow ischemia and reperfusion of the large colon. Am J Vet Res 1995;56:656663.

    • Search Google Scholar
    • Export Citation
  • 44.

    McConnico RS, Argenzio RA, Roberts MC. Prostaglandin E2 and reactive oxygen metabolite damage in the cecum in a pony model of acute colitis. Can J Vet Res 2002;66:5054.

    • Search Google Scholar
    • Export Citation
  • 45.

    Clarke LL, Argenzio RA. NaCl transport across equine proximal colon and the effect of endogenous prostanoids. Am J Physiol 1990;259:G62G69.

    • Search Google Scholar
    • Export Citation
  • 46.

    Richter RA, Freeman DE, Wallig M, et al. In vitro anion transport alterations and apoptosis induced by phenylbutazone in the right dorsal colon of ponies. Am J Vet Res 2002;63:934941.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 47.

    Van Hoogmoed LM, Snyder JR, Harmon F, et al. In vitro investigation of the effect of prostaglandins and nonsteroidal antiinflammatory drugs on contractile activity of the equine smooth muscle of the dorsal colon, ventral colon, and pelvic flexure. Am J Vet Res 2000;61:12591266.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 48.

    Campbell NB, Jones SL, Blikslager AT. The effects of cyclooxygenase inhibitors on bile-injured and normal equine colon. Equine Vet J 2002;34:493498.

    • Search Google Scholar
    • Export Citation
  • 49.

    Wallace JL, Fiorucci S. A magic bullet for mucosal protection … and aspirin is the trigger!. Trends Pharmacol Sci 2003;24:323326.

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