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

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83 Scopus citations

Abstract

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 (US)
Pages (from-to)1311-1322
Number of pages12
JournalGastroenterology
Volume123
Issue number4
DOIs
StatePublished - Oct 1 2002

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Ethridge, R. T., Chung, D. H., Slogoff, M., Ehlers, R. A., Hellmich, M. R., Rajaraman, S., Saito, H., Uchida, T., & Evers, B. M. (2002). Cyclooxygenase-2 gene disruption attenuates the severity of acute pancreatitis and pancreatitis-associated lung injury. Gastroenterology, 123(4), 1311-1322. https://doi.org/10.1053/gast.2002.35951