Inhibition of skin sclerosis by 15deoxy Δ^12,14-prostaglandin J₂ and retrovirally transfected prostaglandin D synthase in a mouse model of bleo

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• 作者：Shizuka Kohno ; Hirahito Endo ; Atsushi Hashimoto ; Izumi Hayashi ; Yusuke Murakami ; Hidero Kitasato ; Fumiaki Kojima ; Shinichi Kawai and Hirobumi Kondo
• 关键词：Scleroderma ; Skin sclerosis ; 15d-PGJ₂ ; PPARγ ; Mast cell
• 刊名：Biomedicine and Pharmacotherapy
• 出版年：2006
• 出版时间：January 2006
• 年：2006
• 卷：60
• 期：1
• 页码：18-25
• 全文大小：543 K

文摘

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-Δ^12,14-prostaglandin J₂ (15d-PGJ₂) or the injection of prostaglandin D₂ synthase (PGDS) cDNA expressing-retrovirally transfected fibroblasts on bleomycin (BLM)-induced scleroderma-like skin sclerosis. Daily injection of BLM (30 μg) for 4 weeks induced histological evidence of dermal sclerosis in C3H mice. We examined the effect of injection of 15d-PGJ₂ (30 ng twice a day) or PGDS expressing-retrovirally transfected fibroblast on BLM-induced dermal sclerosis. Administration of 15d-PGJ₂ (a nonenzymatic metabolite of PGD₂) injection of PGDS cDNA-expressing fibroblasts significantly reduced dermal sclerosis, the hydroxyproline content, and dermal thickness. Moreover, 15-d PGJ2 down-regulation of the expression of transforming growth factor β₁ 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 PGJ₂ and PGDS-expressing cells also suppressed degranulation of cultured mast cells and histamine release by these cells. These results show that 15-d PGJ₂ and PGDS-expressing cells can prevent experimental skin sclerosis induced by BLM and raise the possibility of therapeutic approaches targeting of PPARγ for the skin lesion of scleroderma.