Inhibition of heat-shock protein 70 induction in intestinal cells overexpressing cyclooxygenase 2

R. T. Ethridge, M. R. Hellmich, R. N. DuBois, B. M. Evers

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Background and Aims: The cyclooxygenase (COX) enzymes catalyze the initial step of prostaglandin formation; the inducible form, COX-2, plays a role in inflammation. Heat-shock protein 70 (hsp70) is a stress-responsive gene important for cell survival; induction of hsp70 appears to be mediated, in part, by the prostaglandin pathway. We determined the effect of COX-2 overexpression on hsp70 induction in rat intestinal epithelial (RIE) cells. Methods: RIE cells transfected with COX-2 complementary DNA oriented in the sense (RIE-S) or antisense (RIE-AS) direction were subjected to a heat shock; RNA and protein were harvested and analyzed by Northern and Western blots, respectively. Gel shift assays were performed to assess DNA binding. Results: Both hsp70 messenger RNA and HSP70 protein levels were increased in the RIE- AS cells, whereas induction was markedly inhibited in the RIE-S cells after heat shock. Inhibition of heat-shock factor binding was noted in RIE-S cells, suggesting that heat-shock transcription factor regulation may explain the inhibition of hsp70. The COX-2 selective inhibitor, NS-398, reversed the effects of COX-2 overexpression. Conclusions: The results support a functional role for the prostaglandin/COX pathway in the induction of hsp70. The findings underscore a potential regulatory mechanism involving an inverse relationship between COX-2 expression and hsp70 induction.

Original languageEnglish (US)
Pages (from-to)1454-1463
Number of pages10
JournalGastroenterology
Volume115
Issue number6
StatePublished - 1998
Externally publishedYes

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HSP70 Heat-Shock Proteins
Cyclooxygenase 2
Epithelial Cells
Shock
Hot Temperature
Prostaglandin-Endoperoxide Synthases
Prostaglandins
Cyclooxygenase 2 Inhibitors
Northern Blotting
Cell Survival
Proteins
Complementary DNA
Western Blotting
Gels
RNA
Inflammation
Messenger RNA
DNA
Enzymes
Genes

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Ethridge, R. T., Hellmich, M. R., DuBois, R. N., & Evers, B. M. (1998). Inhibition of heat-shock protein 70 induction in intestinal cells overexpressing cyclooxygenase 2. Gastroenterology, 115(6), 1454-1463.

Inhibition of heat-shock protein 70 induction in intestinal cells overexpressing cyclooxygenase 2. / Ethridge, R. T.; Hellmich, M. R.; DuBois, R. N.; Evers, B. M.

In: Gastroenterology, Vol. 115, No. 6, 1998, p. 1454-1463.

Research output: Contribution to journalArticle

Ethridge, RT, Hellmich, MR, DuBois, RN & Evers, BM 1998, 'Inhibition of heat-shock protein 70 induction in intestinal cells overexpressing cyclooxygenase 2', Gastroenterology, vol. 115, no. 6, pp. 1454-1463.
Ethridge, R. T. ; Hellmich, M. R. ; DuBois, R. N. ; Evers, B. M. / Inhibition of heat-shock protein 70 induction in intestinal cells overexpressing cyclooxygenase 2. In: Gastroenterology. 1998 ; Vol. 115, No. 6. pp. 1454-1463.
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