Reduced expression of 15-PGDH contributes to elevated PGE2 levels in inflamed mucosa of IBD patients

Taisuke Otani, Andrew Dannenberg, Kentaro Yamaguchi, Kazuhiko Yoshimatsu, Kenji Ogawa

Research output: Contribution to journalArticle

Abstract

Increased amounts of prostaglandin (PG) E2 have been detected in the inflamed mucosa of patients with inflammatory bowel disease (IBD). Multiple lines of evidence suggest an important role for PGE2, and increased amounts of PGE2 are detected at sites of intestinal inflammation and correlate with disease activity in IBD. Conversely, PGE2 is important for maintaining mucosal homeostasis. It is important, therefore, to define the pathways that are dysregulated in IBD resulting in increased amounts of mucosal PGE2. PGE2 is catalyzed by cyclooxygenase (COX) and prostaglandin E synthase (PGES) and diminished by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Increased amounts of COX-2 and mPGES-1 have been detected in inflamed mucosa in IBD. In this study, we investigated whether amounts of 15-PGDH were altered in inflamed mucosa from patients with IBD. Reduced amounts of 15-PGDH were detected in inflamed intestinal mucosa from patients with IBD. Because of the importance of tumor necrosis factor-α (TNF-α) in IBD, we also determined the effects of TNF-α on the expression of 15-PGDH in vitro. Treatment with TNF-α increased amounts of PGE2, COX-2 and mPGES-1 protein, but decreased 15-PGDH protein in human colonocytes. Overexpressing 15-PGDH blocked the increase in PGE 2 production mediated by TNF-α. Taken together, these results suggest that reduced expression of 15-PGDH contributes to the elevated levels of PGE2 found in inflamed mucosa of IBD patients. The decrease in amounts of 15-PGDH in inflamed mucosa can be explained at least, in part, by TNF-α-mediated suppression of 15-PGDH transcription.

Original languageEnglish (US)
Pages (from-to)170-175
Number of pages6
JournalBiotherapy
Volume21
Issue number3
StatePublished - May 1 2007

Keywords

  • 15-hydroxyprostaglandin dehydrogenase
  • Inflammatory bowel disease
  • Prostaglandin E
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Cancer Research
  • Immunology and Allergy

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