Unknown

Dataset Information

0

Interferon regulatory factor (IRF)-1 and IRF-2 regulate interferon gamma-dependent cyclooxygenase 2 expression.


ABSTRACT: Cyclooxygenases (Cox) are rate-limiting enzymes that initiate the conversion of arachidonic acid to prostanoids. Cox-2 is the inducible isoform that is upregulated by proinflammatory agents, initiating many prostanoid-mediated pathological aspects of inflammation. In this study, we demonstrate that interferon (IFN)-gamma alone or in synergy with lipopolysaccharide (LPS) or interleukin 1alpha induces Cox-2 expression in mouse peritoneal macrophages, which is paralleled by changes in Cox-2 protein levels and prostaglandin E(2) (PGE(2)) release. Induction of Cox-2 was abrogated in macrophages that lack IFN regulatory factor (IRF)-1, consistent with an attenuated hepatic mRNA response in IRF-1(-/-) mice injected with LPS. Conversely, the absence of IRF-2 in macrophages resulted in a significant increase in both basal and inducible Cox-2 gene and protein expression as well as IFN-gamma-stimulated PGE(2) release, identifying IRF-2 as negative regulator of this promoter. Two IFN stimulation response elements were identified in the mouse Cox-2 promoter that were highly conserved in the human Cox-2 gene. Both bind endogenous IRF-1 and IRF-2 and regulate transcription in an IRF-1/2-dependent manner. Our data demonstrate conclusively the importance of IFN-gamma as a direct activator and coactivator of the Cox-2 gene, and the central role of IRF-1/2 family members in this process.

SUBMITTER: Blanco JC 

PROVIDER: S-EPMC2193204 | biostudies-literature | 2000 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

Interferon regulatory factor (IRF)-1 and IRF-2 regulate interferon gamma-dependent cyclooxygenase 2 expression.

Blanco J C JC   Contursi C C   Salkowski C A CA   DeWitt D L DL   Ozato K K   Vogel S N SN  

The Journal of experimental medicine 20000601 12


Cyclooxygenases (Cox) are rate-limiting enzymes that initiate the conversion of arachidonic acid to prostanoids. Cox-2 is the inducible isoform that is upregulated by proinflammatory agents, initiating many prostanoid-mediated pathological aspects of inflammation. In this study, we demonstrate that interferon (IFN)-gamma alone or in synergy with lipopolysaccharide (LPS) or interleukin 1alpha induces Cox-2 expression in mouse peritoneal macrophages, which is paralleled by changes in Cox-2 protein  ...[more]

Similar Datasets

| S-EPMC10112362 | biostudies-literature
| S-EPMC3093898 | biostudies-other
| S-EPMC3295002 | biostudies-literature
| S-EPMC1143633 | biostudies-literature
| S-EPMC1219763 | biostudies-other
| S-EPMC6912676 | biostudies-literature
| S-EPMC395418 | biostudies-other
| S-EPMC3514179 | biostudies-literature
| S-EPMC1221234 | biostudies-other
| S-EPMC3406097 | biostudies-literature