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Mutual Antagonistic Relationship Between Prostaglandin E2 and Interferon-(gamma): Implications for Rheumatoid Arthritis


ABSTRACT: PGE2 is a major mediator of inflammation and is present at high concentrations in the synovial fluid of rheumatoid arthritis (RA) patients. PGE2, acting through the EP4 receptor, has both pro- and anti-inflammatory roles in vivo. To shed light on this dual role of PGE2, we investigated its effects in whole blood and in primary human fibroblast-like synoviocytes. Gene expression analysis in human leukocytes, confirmed at the protein level, revealed an EP4-dependent inhibition of the expression of genes involved in the IFN-gamma activation pathway, including IFN-gamma itself. This effect of the PGE2/EP4 axis on IFN-gamma is a reciprocal phenomenon since IFN-gamma blocks PGE2 release and blocks EP receptor expression. The mutually antagonistic relationship between IFN-gamma and PGE2 extends to downstream cytokine- and chemokine-release; PGE2 counters the effects of IFN-gamma, on the release of IP-10, IL-8, TNFalpha and IL-1beta. To gain further insight into IFN-gamma-mediated cellular events in rheumatoid arthritis, we assessed the effects of IFN-gamma on gene expression in fibroblast-like synoviocytes. We observed an IFN-gamma-dependent up-regulation of macrophage-attracting chemokines, and down-regulation of metalloprotease expression. These results suggest the existence of a mutually antagonistic relationship between PGE2 and IFN-gamma which may represent a fundamental mechanism of immune control in diseases such as RA. For details, see Mathieu MC et al, EJI, issue 7, 2008

ORGANISM(S): Homo sapiens

SUBMITTER: Alex Therien 

PROVIDER: E-GEOD-11575 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Mutual antagonistic relationship between prostaglandin E(2) and IFN-gamma: Implications for rheumatoid arthritis.

Mathieu Marie-Claude MC   Lord-Dufour Simon S   Bernier Virginie V   Boie Yves Y   Burch Jason D JD   Clark Patsy P   Denis Danielle D   Han Yongxin Y   Mortimer James R JR   Therien Alex G AG  

European journal of immunology 20080701 7


Prostaglandin E(2) (PGE(2)) is a major mediator of inflammation and is present at high concentrations in the synovial fluid of rheumatoid arthritis (RA) patients. PGE(2), acting through the EP4 receptor, has both pro- and anti-inflammatory roles in vivo. To shed light on this dual role of PGE(2), we investigated its effects in whole blood and in primary human fibroblast-like synoviocytes (FLS). Gene expression analysis in human leukocytes, confirmed at the protein level, revealed an EP4-dependen  ...[more]

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