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Fluid Secretion Caused by Aerolysin-Like Hemolysin of Aeromonas sobria in the Intestines Is Due to Stimulation of Production of Prostaglandin E2 via Cyclooxygenase 2 by Intestinal Cells▿

By Yoshio Fujii, Ken Tsurumi, Masaaki Sato, Eizo Takahashi and Keinosuke Okamoto


To clarify the mechanisms of diarrheal disease induced by Aeromonas sobria, we examined whether prostaglandin E2 (PGE2) was involved in the intestinal secretory action of A. sobria hemolysin by use of a mouse intestinal loop model. The amount of PGE2 in jejunal fluid and the fluid accumulation ratio were directly related to the dose of hemolysin. The increase over time in the level of PGE2 was similar to that of the accumulated fluid. In addition, hemolysin-induced fluid secretion and PGE2 synthesis were inhibited by the selective cyclooxygenase 2 (COX-2) inhibitor NS-398 but not the COX-1 inhibitor SC-560. Western blot analysis revealed that hemolysin increased the COX-2 protein levels but reduced the COX-1 protein levels in mouse intestinal mucosa in vivo. These results suggest that PGE2 functions as an important mediator of diarrhea caused by hemolysin and that PGE2 is produced primarily through a COX-2-dependent mechanism. Subsequently, we examined the relationship between PGE2, cyclic AMP (cAMP), and cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channels in mouse intestinal mucosa exposed to hemolysin. Hemolysin increased the levels of cAMP in the intestinal mucosa. NS-398 inhibited the increase in cAMP production, but SC-560 did not. In addition, H-89, a cAMP-dependent protein kinase A (PKA) inhibitor, and glibenclamide, a CFTR inhibitor, inhibited fluid accumulation. Taken together, these results indicate that hemolysin activates PGE2 production via COX-2 and that PGE2 stimulates cAMP production. cAMP then activates PKA, which in turn stimulates CFTR Cl− channels and finally leads to fluid accumulation in the intestines

Topics: Molecular Pathogenesis
Publisher: American Society for Microbiology (ASM)
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Provided by: PubMed Central
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