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2001 Abstract: 1797 COX-2 Gene Disruption Results in the Attenuation of HSP70 Expression Following Acute Pancreatitis

2001 Digestive Disease Week

# 1797 COX-2 Gene Disruption Results in the Attenuation of HSP70 Expression Following Acute Pancreatitis
Richard T. Ethridge, Koji Hashimoto, Dai H. Chung, Mark R. Hellmich, B. Mark Evers, Galveston, TX

BACKGROUND. The prostaglandin synthase-2 (ie, cyclooxygenase [COX]-2) isoform plays an important role in a number of inflammatory processes. We have recently shown that COX-2 expression is increased following acute pancreatitis (AP); selective inhibition or disruption of the COX-2 gene (ptgs2) results in a marked attenuation in the severity of AP. Heat shock proteins (HSPs) are a family of protective proteins that are induced following stress or injury (eg, AP); the relationship of COX-2 and HSP70 following induction of AP is currently unknown. The purpose of this study was to determine the relationship of COX-2 and HSP70 expression using a secretagogue (caerulein [CAE])-induced model of AP.

METHODS. Wild type (ptgs2+/+) and knockout (ptgs2-/-) mice were injected (i.p.) with either saline or CAE (50 mg/kg) hourly for 8 h; mice were sacrificed at 1 h after induction of AP, and pancreata harvested and protein extracted. Western blots were performed to determine the expression of the HSPs (70, 27, 60, and 90); blots were stripped and reprobed with the heat shock constitutive (HSC)70 protein as a control for loading. Electrophoretic mobility shift assays (EMSAs) were performed to assess the DNA-binding activity of heat shock factor (HSF), which regulates HSP70 expression.

RESULTS. Induction of HSP70 expression was noted in the pancreas of wild type mice as we have previously shown; in contrast, HSP70 levels were not increased in the pancreas of ptgs2-/- mice following CAE injections. The expression of HSP27, 60, and 90 was not altered in the two groups of mice. EMSAs demonstrated induction of HSF binding activity in wild type mice but not in the ptgs2-/- mice.

CONCLUSIONS. Deletion of the ptgs2 gene results in the inhibition of HSP70 protein expression following AP; this decreased expression is likely due to the decreased binding activity of the HSF transcription factor.

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