マウス骨芽細胞MC3T3-E1における脂肪酸シクロオキシゲナーゼの誘導

概要

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Fatty acid cyclooxygenase transforms arachidonic acid to prostaglandin (PG) H_2, which is a precursor for various bioactive prostaglandins and thromboxanes. Recent studies have demonstrated the occurrence of two isozymes of the cyclooxygenase enzymes (COX-1 and COX-2). COX-1 is a constitutive enzyme, which is found in many mammalian tissues and engaged in various house-keeping functions there. In contrast, COX-2 is a product of an immediate early gene, and induced rapidly and transiently in certain types of cell. An osteoblastic cell line MC3T3-E1 produced PGE_2 from a arachidonic acid, and its cyclooxygenase enzyme was induced by EGF, TGFβ, TNFα, epinephrine and prostaglandins with a lag phase of 1-2 h. Several lines of evidence indicated the identity of the induced enzyme as COX-2 isoform. The mechanism of transcriptional regulation of the COX-2 gene was investigated with TNFα as an inducer. The 5'-flanking region of the COX-2 gene was cloned, and shown by deletion analyses to include two positive regions with NFκB and NF-IL6 elements. Point mutations of these elements and gel shift assays suggested a potential role of both NFκB and NF-IL6 in the TNFα-dependent induction of COX-2 in MC3T3-E1 cells.
日本ビタミン学会の論文
1996-10-25