Proinflammatory cytokines regulate cyclooxygenase-2 mRNA expression in human macrophages.

Abstract:

:Prostaglandins play a major role in the inflammatory and immune response. Macrophages constitutively produce prostaglandins by the enzyme cyclooxygenase-1 (cox) whereas inflammatory mediators and cytokines stimulate the inducible enzyme cox-2 for high output prostaglandin production. In this study, we investigated the effect of LPS, IFN-gamma and TNF-alpha in the regulation of cox-1 and cox-2 mRNA expression in PMA-differentiated U937 human macrophages. LPS, but not IFN-gamma or TNF-alpha, caused the induction of cox-2 mRNA in a dose- and time-dependent fashion. In IFN-gamma-primed macrophages, LPS stimulated a marked increase in the accumulation of cox-2 mRNA, whereas TNF-alpha and IFN-gamma induced a moderate level. However, IFN-gamma in combination with either LPS or TNF-alpha induced a synergistic increase in the accumulation of cox-2 mRNA after 24 hours. Regardless of the conditions, cox-1 mRNA remained unchanged. These results indicate that IFN-gamma priming is required for full expression of cox-2 mRNA in response to LPS or TNF-alpha stimulation and suggest that cox-2 mRNA is highly regulated by cytokines during macrophage activation.

authors

Arias-Negrete S,Keller K,Chadee K

doi

10.1006/bbrc.1995.1378

subject

Has Abstract

pub_date

1995-03-17 00:00:00

pages

582-9

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006291X85713782

journal_volume

208

pub_type

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