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. 1997 Oct 15;100(8):1928–1933. doi: 10.1172/JCI119723

Prostaglandins I2 and E2 have a synergistic role in rescuing epithelial barrier function in porcine ileum.

A T Blikslager 1, M C Roberts 1, J M Rhoads 1, R A Argenzio 1
PMCID: PMC508381  PMID: 9329955

Abstract

Prostaglandins (PG) are cytoprotective for gastrointestinal epithelium, possibly because they enhance mucosal repair. The objective of the present studies was to assess the role of prostaglandins in intestinal repair. Intestinal mucosa from porcine ileum subjected to 1 h of ischemia was mounted in Ussing chambers. Recovery of normal transepithelial electrical resistance occurred within 2 h, and continued to increase for a further 2 h to a value twice that of control. The latter response was blocked by inhibition of prostaglandin synthesis, and restored by addition of both carbacyclin (an analog of PGI2) and PGE2, whereas the addition of each alone had little effect. Histologically, prostaglandins had no effect on epithelial restitution or villous contraction, indicating that elevations in transepithelial resistance were associated with increases in paracellular resistance. Furthermore, prostaglandin-stimulated elevations in resistance were inhibited with cytochalasin D, an agent known to stimulate cytoskeletal contraction. Synergistic elevations in transepithelial resistance, similar to those of carbacyclin and PGE2, were also noted after treatment with cAMP and A23187 (a calcium ionophore). We conclude that PGE2 and PGI2 have a synergistic role in restoration of intestinal barrier function by increasing intracellular cAMP and Ca2+, respectively, which in turn signal cytoskeletal-mediated tight junction closure.

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Selected References

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  1. Anderson J. M., Van Itallie C. M. Tight junctions and the molecular basis for regulation of paracellular permeability. Am J Physiol. 1995 Oct;269(4 Pt 1):G467–G475. doi: 10.1152/ajpgi.1995.269.4.G467. [DOI] [PubMed] [Google Scholar]
  2. Argenzio R. A., Armstrong M., Rhoads J. M. Role of the enteric nervous system in piglet cryptosporidiosis. J Pharmacol Exp Ther. 1996 Dec;279(3):1109–1115. [PubMed] [Google Scholar]
  3. Argenzio R. A., Lecce J., Powell D. W. Prostanoids inhibit intestinal NaCl absorption in experimental porcine cryptosporidiosis. Gastroenterology. 1993 Feb;104(2):440–447. doi: 10.1016/0016-5085(93)90412-6. [DOI] [PubMed] [Google Scholar]
  4. Di Marzo V. Arachidonic acid and eicosanoids as targets and effectors in second messenger interactions. Prostaglandins Leukot Essent Fatty Acids. 1995 Oct;53(4):239–254. doi: 10.1016/0952-3278(95)90123-x. [DOI] [PubMed] [Google Scholar]
  5. Duffey M. E., Hainau B., Ho S., Bentzel C. J. Regulation of epithelial tight junction permeability by cyclic AMP. Nature. 1981 Dec 3;294(5840):451–453. doi: 10.1038/294451a0. [DOI] [PubMed] [Google Scholar]
  6. Eberhart C. E., Dubois R. N. Eicosanoids and the gastrointestinal tract. Gastroenterology. 1995 Jul;109(1):285–301. doi: 10.1016/0016-5085(95)90296-1. [DOI] [PubMed] [Google Scholar]
  7. Erickson R. A., Tarnawski A., Dines G., Stachura J. 16,16-Dimethyl prostaglandin E2 induces villus contraction in rats without affecting intestinal restitution. Gastroenterology. 1990 Sep;99(3):708–716. doi: 10.1016/0016-5085(90)90959-5. [DOI] [PubMed] [Google Scholar]
  8. Gyires K. Some of the factors that may mediate or modify the gastrointestinal mucosal damage induced by non-steroidal anti-inflammatory drugs. Agents Actions. 1994 Mar;41(1-2):73–79. doi: 10.1007/BF01986397. [DOI] [PubMed] [Google Scholar]
  9. Hawkey C. J., Rampton D. S. Prostaglandins and the gastrointestinal mucosa: are they important in its function, disease, or treatment? Gastroenterology. 1985 Nov;89(5):1162–1188. doi: 10.1016/0016-5085(85)90225-2. [DOI] [PubMed] [Google Scholar]
  10. Jacobson E. D. Circulatory mechanisms of gastric mucosal damage and protection. Gastroenterology. 1992 May;102(5):1788–1800. doi: 10.1016/0016-5085(92)91745-p. [DOI] [PubMed] [Google Scholar]
  11. Lauritsen K., Laursen L. S., Bukhave K., Rask-Madsen J. In vivo profiles of eicosanoids in ulcerative colitis, Crohn's colitis, and Clostridium difficile colitis. Gastroenterology. 1988 Jul;95(1):11–17. doi: 10.1016/0016-5085(88)90284-3. [DOI] [PubMed] [Google Scholar]
  12. Madara J. L. Increases in guinea pig small intestinal transepithelial resistance induced by osmotic loads are accompanied by rapid alterations in absorptive-cell tight-junction structure. J Cell Biol. 1983 Jul;97(1):125–136. doi: 10.1083/jcb.97.1.125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Madara J. L. Loosening tight junctions. Lessons from the intestine. J Clin Invest. 1989 Apr;83(4):1089–1094. doi: 10.1172/JCI113987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Madara J. L., Moore R., Carlson S. Alteration of intestinal tight junction structure and permeability by cytoskeletal contraction. Am J Physiol. 1987 Dec;253(6 Pt 1):C854–C861. doi: 10.1152/ajpcell.1987.253.6.C854. [DOI] [PubMed] [Google Scholar]
  15. Madara J. L., Stafford J. Interferon-gamma directly affects barrier function of cultured intestinal epithelial monolayers. J Clin Invest. 1989 Feb;83(2):724–727. doi: 10.1172/JCI113938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McCormack S. A., Viar M. J., Johnson L. R. Migration of IEC-6 cells: a model for mucosal healing. Am J Physiol. 1992 Sep;263(3 Pt 1):G426–G435. doi: 10.1152/ajpgi.1992.263.3.G426. [DOI] [PubMed] [Google Scholar]
  17. Miller T. A. Protective effects of prostaglandins against gastric mucosal damage: current knowledge and proposed mechanisms. Am J Physiol. 1983 Nov;245(5 Pt 1):G601–G623. doi: 10.1152/ajpgi.1983.245.5.G601. [DOI] [PubMed] [Google Scholar]
  18. Moore R., Carlson S., Madara J. L. Villus contraction aids repair of intestinal epithelium after injury. Am J Physiol. 1989 Aug;257(2 Pt 1):G274–G283. doi: 10.1152/ajpgi.1989.257.2.G274. [DOI] [PubMed] [Google Scholar]
  19. Palant C. E., Duffey M. E., Mookerjee B. K., Ho S., Bentzel C. J. Ca2+ regulation of tight-junction permeability and structure in Necturus gallbladder. Am J Physiol. 1983 Sep;245(3):C203–C212. doi: 10.1152/ajpcell.1983.245.3.C203. [DOI] [PubMed] [Google Scholar]
  20. Paradiso A. M., Cheng E. H., Boucher R. C. Effects of bradykinin on intracellular calcium regulation in human ciliated airway epithelium. Am J Physiol. 1991 Aug;261(2 Pt 1):L63–L69. doi: 10.1152/ajplung.1991.261.2.L63. [DOI] [PubMed] [Google Scholar]
  21. Rhoads J. M., Chen W., Chu P., Berschneider H. M., Argenzio R. A., Paradiso A. M. L-glutamine and L-asparagine stimulate Na+ -H+ exchange in porcine jejunal enterocytes. Am J Physiol. 1994 May;266(5 Pt 1):G828–G838. doi: 10.1152/ajpgi.1994.266.5.G828. [DOI] [PubMed] [Google Scholar]
  22. Robert A. Cytoprotection by prostaglandins. Gastroenterology. 1979 Oct;77(4 Pt 1):761–767. [PubMed] [Google Scholar]
  23. Shasby D. M., Kamath J. M., Moy A. B., Shasby S. S. Ionomycin and PDBU increase MDCK monolayer permeability independently of myosin light chain phosphorylation. Am J Physiol. 1995 Aug;269(2 Pt 1):L144–L150. doi: 10.1152/ajplung.1995.269.2.L144. [DOI] [PubMed] [Google Scholar]
  24. Zushi S., Shinomura Y., Kiyohara T., Minami T., Sugimachi M., Higashimoto Y., Kanayama S., Matsuzawa Y. Role of prostaglandins in intestinal epithelial restitution stimulated by growth factors. Am J Physiol. 1996 May;270(5 Pt 1):G757–G762. doi: 10.1152/ajpgi.1996.270.5.G757. [DOI] [PubMed] [Google Scholar]

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