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A novel anti‐inflammatory role for secretory phospholipase A2 in immune complex‐mediated arthritis
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A novel anti‐inflammatory role for secretory phospholipase A2 in immune complex‐mediated arthritis
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Journal Article
A novel anti‐inflammatory role for secretory phospholipase A2 in immune complex‐mediated arthritis
2010
Overview
Phospholipase A
2
(PLA
2
) catalyses the release of arachidonic acid for generation of lipid mediators of inflammation and is crucial in diverse inflammatory processes. The functions of the secretory PLA
2
enzymes (sPLA
2
), numbering nine members in humans, are poorly understood, though they have been shown to participate in lipid mediator generation and the associated inflammation. To further understand the roles of sPLA
2
in disease, we quantified the expression of these enzymes in the synovial fluid in rheumatoid arthritis and used gene‐deleted mice to examine their contribution in a mouse model of autoimmune erosive inflammatory arthritis. Contrary to expectation, we find that the group V sPLA
2
isoform plays a novel anti‐inflammatory role that opposes the pro‐inflammatory activity of group IIA sPLA
2
. Mechanistically, group V sPLA
2
counter‐regulation includes promotion of immune complex clearance by regulating cysteinyl leukotriene synthesis. These observations identify a novel anti‐inflammatory function for a PLA
2
and identify group V sPLA
2
as a potential biotherapeutic for treatment of immune‐complex‐mediated inflammation.
Publisher
Nature Publishing Group UK,WILEY‐VCH Verlag,Wiley Open Access,WILEY-VCH Verlag
Subject
/ Anti-Inflammatory Agents - immunology
/ Antigen-Antibody Complex - immunology
/ Arthritis, Rheumatoid - enzymology
/ Arthritis, Rheumatoid - genetics
/ Arthritis, Rheumatoid - immunology
/ Female
/ Humans
/ Male
/ Mice
/ Phospholipases A2, Secretory - genetics
