Inhibition of skin sclerosis by 15deoxy Δ12,14-prostaglandin J2 and retrovirally transfected prostaglandin D synthase in a mouse model of bleomycin-induced scleroderma
Inhibition of skin sclerosis by 15deoxy Δ12,14-prostaglandin J2 and retrovirally transfected prostaglandin D synthase in a mouse model of bleomycin-induced scleroderma
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DOI：
10.1016/j.biopha.2005.04.004
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发表时间：
2006-01-01
影响因子：
7.5
通讯作者：
Kondo, H
中科院分区：
文献类型：
--
作者：
Kohno, S;Endo, H;Kondo, H
造血前列腺素D合成酶（PGDS）是参与PGD和J系列产生的关键酶，其在炎症和免疫中具有多种作用。我们评价了15-脱氧-δ（12，14）-前列腺素J（2）（15 d-PGJ（2））或注射表达前列腺素D-2合酶（PGDS）cDNA的逆转录病毒转染成纤维细胞对博莱霉素（BLM）诱导的硬皮病样皮肤硬化的作用。每天注射BLM（30 μ g）4周诱导C3 H小鼠皮肤硬化的组织学证据。我们检测了注射15 d-PGJ（2）（30 ng，每天两次）或表达PGDS的逆转录病毒转染的成纤维细胞对BLM诱导的皮肤硬化的影响。注射表达PGDS cDNA的成纤维细胞的15 d-PGJ 2（PGD（2）的非酶代谢产物）显著减少了真皮硬化、羟脯氨酸含量和真皮厚度。15 d PGJ（2）下调BLM诱导的转化生长因子β 1和结缔组织生长因子的表达。肥大细胞也增加了皮肤中的BLM注射，并有显着的脱粒这些肥大细胞沿着血浆组胺水平升高。15-d PGJ（2）和PGDS表达细胞也抑制培养的肥大细胞的脱粒和这些细胞释放组胺。这些结果表明，表达15-d PGJ（2）和PGDS的细胞可以预防BLM诱导的实验性皮肤硬化，并提高了以PPAR γ为靶点治疗硬皮病皮肤病变的可能性。(c)2005年，Elsevier SAS。All rights reserved.
Hematopoietic prostaglandin D synthase (PGDS) is a key enzyme involved in production of the PGD and J series, which have various role in inflammation and immunity. We evaluated the effect of treatment with 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) or the injection of prostaglandin D-2 synthase (PGDS) cDNA expressing-retrovirally transfected fibroblasts on bleomycin (BLM)-induced scleroderma-like skin sclerosis. Daily injection of BLM (30 mu g) for 4 weeks induced histological evidence of dermal sclerosis in C3H mice. We examined the effect of injection of 15d-PGJ(2) (30 ng twice a day) or PGDS expressing-retrovirally transfected fibroblast on BLM-induced dermal sclerosis. Administration of 15d-PGJ2 (a nonenzymatic metabolite of PGD(2)) injection of PGDS cDNA-expressing fibroblasts significantly reduced dermal sclerosis, the hydroxyproline content, and dermal thickness. Moreover, 15-d PGJ(2) down-regulation of the expression of transforming growth factor beta 1 and connective tissue growth factor which had been induced by BLM. Mast cells were also increased in the skin by BLM injection and there was prominent degranulation of these mast cells along with elevated plasma histamine levels. 15-d PGJ(2) and PGDS-expressing cells also suppressed degranulation of cultured mast cells and histamine release by these cells. These results show that 15-d PGJ(2) and PGDS-expressing cells can prevent experimental skin sclerosis induced by BLM and raise the possibility of therapeutic approaches targeting of PPAR gamma for the skin lesion of scleroderma. (c) 2005 Elsevier SAS. All rights reserved.