Murakami Yousuke, Akahoshi Tohru, Hayashi Izumi, Endo Hirahito, Hashimoto Atsushi, Kono Shizuka, Kondo Hirobumi, Kawai Shinichi, Inoue Matsuhisa, Kitasato Hidero
Kitasato University School of Medicine, Sagamihara, Japan.
Arthritis Rheum. 2003 Oct;48(10):2931-41. doi: 10.1002/art.11271.
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.
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.
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.
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.
造血前列腺素D合成酶（H-PGDS）是前列腺素D及其J系列代谢产物生成过程中的关键酶。我们评估了逆转录病毒转染的H-PGDS的抗炎作用，以研究H-PGDS在尿酸单钠（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袋模型中内源性PGDS的表达。将H-PGDS互补DNA（cDNA）逆转录病毒转染到C57BL/6J成纤维细胞中，这些细胞被命名为C57-PGDS细胞。通过酶免疫测定法测量C57-PGDS细胞产生前列腺素的情况。研究了C57-PGDS细胞对晶体诱导炎症的影响。
注射晶体导致浸润细胞和气袋周围软组织中H-PGDS表达迅速下降。相反，在炎症早期，白细胞介素-1β（IL-1β）和巨噬细胞炎性蛋白2（MIP-2）的表达以及细胞浸润显著增加。C57-PGDS细胞而非对照细胞在体外产生的前列腺素D2（PGD2）量增加，但抑制了前列腺素E2（PGE2）的产生。将C57-PGDS细胞注射到气袋中可抑制细胞浸润以及MIP-2和IL-1β的表达。
在这个MSU晶体诱导炎症的小鼠气袋模型中，逆转录病毒转染的H-PGDS cDNA至少部分通过抑制MIP-2和IL-1β可减少细胞浸润。这些发现表明用H-PGDS进行基因治疗可能对治疗炎症性疾病有用。
