Cyclooxygenase-2 gene disruption attenuates the severity of acute pancreatitis and pancreatitis-associated lung injury

Richard T. Ethridge, Dai H. Chung, Michele Slogoff, Richard A. Ehlers, Mark R. Hellmich, Srinivasan Rajaraman, Hiroshi Saito, Tatsuo Uchida, B. Mark Evers

Research output: Contribution to journalArticlepeer-review

101 Scopus citations


Background and Aims: Cyclooxygenase (COX) catalyzes the rate-limiting step in prostaglandin production; the inducible isoform, COX-2, has been implicated in a variety of inflammatory processes. The role of COX in acute pancreatitis and pancreatitis-associated lung injury is not known. Methods: Acute pancreatitis was induced in Swiss Webster mice or mice deficient in the COX-2 (Ptgs2) or the COX-1 (Ptgs1) genes. Pancreata and lungs were harvested, and histologic sections of these tissues were scored. COX-2 expression, myeloperoxidase activity (a measurement of neutrophil sequestration), and serum amylase levels were determined. Results: Acute pancreatitis was associated with induction of COX-2 expression. Treatment with NS-398 (a COX-2 inhibitor) significantly decreased the severity of pancreatitis. Furthermore, Ptgs2-deficient mice showed minimal histologic evidence of pancreatitis, a marked attenuation in the severity of lung injury, and a significant reduction in myeloperoxidase activity. In contrast, Ptgs1-deficient mice had pancreatitis and pulmonary inflammation, which was as severe or, in some instances, more severe than in the wild-type mice. Conclusions: Inhibition of COX-2 by either pharmacologic inhibition or selective genetic deletion markedly attenuated the severity of acute pancreatitis. Our findings identify the COX-2 isoform as an important regulator of the severity of acute pancreatitis and pancreatitis-associated lung injury.

Original languageEnglish
Pages (from-to)1311-1322
Number of pages12
Issue number4
StatePublished - Oct 1 2002

Bibliographical note

Funding Information:
Supported by grants from the National Institutes of Health (PO1 DK35608, RO1 DK48498, and T32 DK07639). R.T.E. is a recipient of a National Alpha Omega Alpha Student Research Fellowship and a McLaughlin Fellowship Award. R.A.E. is a recipient of an Individual Research Service Award (F32 CA79187) and a Jeane B. Kempner Award.

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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