RRC ID 78044
Author Murakami Y, Akahoshi T, Hayashi I, Endo H, Hashimoto A, Kono S, Kondo H, Kawai S, Inoue M, Kitasato H.
Title Inhibition of monosodium urate monohydrate crystal-induced acute inflammation by retrovirally transfected prostaglandin D synthase.
Journal Arthritis Rheum
Abstract OBJECTIVE:Hematopoietic prostaglandin D synthase (H-PGDS) is a key enzyme in the production of prostaglandin D and its J series metabolites. We evaluated the antiinflammatory effect of retrovirally transfected H-PGDS in order to investigate the role of H-PGDS in monosodium urate monohydrate (MSU) crystal-induced acute inflammation.
METHODS:Expression of endogenous PGDS in a murine air-pouch model of MSU crystal-induced acute inflammation was determined by real-time polymerase chain reaction. H-PGDS complementary DNA (cDNA) was retrovirally transfected into C57BL/6J fibroblasts, and the cells were designated as C57-PGDS cells. Production of prostaglandins by C57-PGDS cells was measured by enzyme immunoassay. The effect of C57-PGDS cells on crystal-induced inflammation was investigated.
RESULTS:Injection of the crystals caused a rapid decrease in H-PGDS expression by infiltrating cells and by the soft tissues around the air pouches. In contrast, expression of interleukin-1beta (IL-1beta) and macrophage inflammatory protein 2 (MIP-2) as well as cellular infiltration were significantly increased during the early stage of inflammation. C57-PGDS cells, but not control cells, produced an increased amount of PGD(2) in vitro, but suppressed production of PGE(2). Injection of C57-PGDS cells into air pouches inhibited cellular infiltration and MIP-2 and IL-1beta expression.
CONCLUSION:In this murine air-pouch model of MSU crystal-induced inflammation, retrovirally transfected H-PGDS cDNA could reduce cellular infiltration, at least partly by inhibiting MIP-2 and IL-1beta. These findings suggest that gene therapy with H-PGDS may be useful for treating inflammatory diseases.
Volume 48(10)
Pages 2931-41
Published 2003-10-1
DOI 10.1002/art.11271
PMID 14558100
MeSH Acute Disease Animals Arthritis, Gouty / immunology Arthritis, Gouty / therapy* Cell Line, Tumor Chemokine CXCL2 Chemokines / genetics Crystallization Disease Models, Animal Fibroblasts / cytology Gene Expression Regulation, Enzymologic Genetic Therapy* Interleukin-1 / genetics Intramolecular Oxidoreductases / genetics* Leukemia, Basophilic, Acute Lipocalins Macrophages / cytology Male Mice Mice, Inbred C57BL Prostaglandin D2 / analogs & derivatives* Prostaglandin D2 / metabolism Rats Retroviridae / genetics* Transfection Uric Acid / chemistry Uric Acid / immunology*
Human and Animal Cells J774.1(RCB0434)