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 Hellmich, Srinivasan Rajaraman, Hiroshi Saito, Tatsuo Uchida, B. Mark Evers

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75 Citations (Scopus)

Abstract

Background & 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

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Lung Injury
Cyclooxygenase 2
Pancreatitis
Genes
Prostaglandin-Endoperoxide Synthases
Peroxidase
Protein Isoforms
Cyclooxygenase 1
Cyclooxygenase 2 Inhibitors
Amylases
Prostaglandins
Pancreas
Pneumonia
Neutrophils
Lung

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Cyclooxygenase-2 gene disruption attenuates the severity of acute pancreatitis and pancreatitis-associated lung injury. / Ethridge, Richard T.; Chung, Dai H.; Slogoff, Michele; Ehlers, Richard A.; Hellmich, Mark; Rajaraman, Srinivasan; Saito, Hiroshi; Uchida, Tatsuo; Evers, B. Mark.

In: Gastroenterology, Vol. 123, No. 4, 01.10.2002, p. 1311-1322.

Research output: Contribution to journalArticle

Ethridge, RT, Chung, DH, Slogoff, M, Ehlers, RA, Hellmich, M, Rajaraman, S, Saito, H, Uchida, T & Evers, BM 2002, 'Cyclooxygenase-2 gene disruption attenuates the severity of acute pancreatitis and pancreatitis-associated lung injury', Gastroenterology, vol. 123, no. 4, pp. 1311-1322. https://doi.org/10.1053/gast.2002.35951
Ethridge, Richard T. ; Chung, Dai H. ; Slogoff, Michele ; Ehlers, Richard A. ; Hellmich, Mark ; Rajaraman, Srinivasan ; Saito, Hiroshi ; Uchida, Tatsuo ; Evers, B. Mark. / Cyclooxygenase-2 gene disruption attenuates the severity of acute pancreatitis and pancreatitis-associated lung injury. In: Gastroenterology. 2002 ; Vol. 123, No. 4. pp. 1311-1322.
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