Defective generation of a humoral immune response is associated with a reduced incidence and severity of collagen-induced arthritis in microsomal prostaglandin E synthase-1 null mice.

Kojima F, Kapoor M, Yang L, Fleishaker EL, Ward MR, Monrad SU, Kottangada PC, Pace CQ, Clark JA, Woodward JG, Crofford LJ
J Immunol. 2008 180 (12): 8361-8

PMID: 18523303 · PMCID: PMC2435291 · DOI:10.4049/jimmunol.180.12.8361

Microsomal PGE synthase-1 (mPGES-1) is an inducible enzyme that acts downstream of cyclooxygenase and specifically catalyzes the conversion of PGH(2) to PGE(2). The present study demonstrates the effect of genetic deletion of mPGES-1 on the developing immunologic responses and its impact on the clinical model of bovine collagen-induced arthritis. mPGES-1 null and heterozygous mice exhibited decreased incidence and severity of arthritis compared with wild-type mice in a gene dose-dependent manner. Histopathological examination revealed significant reduction in lining hyperplasia and tissue destruction in mPGES-1 null mice compared with their wild-type littermates. mPGES-1 deficient mice also exhibited attenuation of mechanical nociception in a gene dose-dependent manner. In addition, mPGES-1 null and heterozygous mice showed a marked reduction of serum IgG against type II collagen, including subclasses IgG1, IgG2a, IgG2b, IgG2c, and IgG3, compared with wild-type mice, which correlated with the reduction in observed inflammatory features. These results demonstrate for the first time that deficiency of mPGES-1 inhibits the development of collagen-induced arthritis, at least in part, by blocking the development of a humoral immune response against type II collagen. Pharmacologic inhibition of mPGES-1 may therefore impact both the inflammation and the autoimmunity associated with human diseases such as rheumatoid arthritis.

MeSH Terms (20)

Animals Arthritis, Experimental Cattle Collagen Type II Cyclooxygenase 1 Cyclooxygenase 2 Female Gene Deletion Genetic Carrier Screening Immunoglobulin G Immunoglobulin M Incidence Male Membrane Proteins Mice Mice, Inbred DBA Mice, Knockout Microsomes RNA, Messenger Severity of Illness Index

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