論文 - 詳細
| RRC ID | 78044 |
|---|---|
| 著者 | Murakami Y, Akahoshi T, Hayashi I, Endo H, Hashimoto A, Kono S, Kondo H, Kawai S, Inoue M, Kitasato H. |
| タイトル | Inhibition of monosodium urate monohydrate crystal-induced acute inflammation by retrovirally transfected prostaglandin D synthase. |
| ジャーナル | 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. |
| 巻・号 | 48(10) |
| ページ | 2931-41 |
| 公開日 | 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* |
| リソース情報 | |
| ヒト・動物細胞 | J774.1(RCB0434) |