Inhibition of monosodium urate monohydrate crystal-induced acute inflammation by retrovirally transfected prostaglandin D synthase
Inhibition of monosodium urate monohydrate crystal-induced acute inflammation by retrovirally transfected prostaglandin D synthase
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DOI：
10.1002/art.11271
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发表时间：
2003-10-01
影响因子：
--
通讯作者：
Kitasato, H
中科院分区：
文献类型：
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作者：
Murakami, Y;Akahoshi, T;Kitasato, H
Objective.造血前列腺素D合成酶（H-PGDS）是产生前列腺素D及其J系列代谢产物的关键酶。我们评价了逆转录病毒转染的H-PGDS的抗炎作用，以研究H-PGDS在一水异戊尿酸（MSU）晶体诱导的急性炎症中的作用。通过实时聚合酶链反应测定MSU晶体诱导的急性炎症小鼠气囊模型中内源性PGDS的表达。将H-PGDS互补DNA（cDNA）逆转录病毒转染C57 BL/6 J成纤维细胞，命名为C57-PGDS细胞。通过酶免疫测定法测量C57-PGDS细胞前列腺素的产生。研究C57-PGDS细胞对晶体诱导的炎症的影响。注射的晶体引起的H-PGDS表达的浸润细胞和周围的气囊软组织的快速下降。与此相反，白细胞介素-1 β（IL-1 β）和巨噬细胞炎性蛋白2（MIP-2）的表达以及细胞浸润在炎症早期显著增加。C57-PGDS细胞，而不是对照细胞，在体外产生增加量的PGD（2），但抑制PGE（2）的产生。将C57-PGDS细胞注入气囊内可抑制细胞浸润和MIP-2及IL-1 β的表达。在MSU晶体诱导炎症的小鼠气囊模型中，逆转录病毒转染的H-PGDS cDNA可以减少细胞浸润，至少部分是通过抑制MIP-2和IL-1 β。这些发现表明，H-PGDS的基因治疗可能有助于治疗炎症性疾病。
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.