Rat fibroblasts synthesize T-kininogen in response to cyclic-AMP, prostaglandin E2 and cytokines.
T-Kininogen is a plasma protein characterized as a kinin-precursor, a cysteine protease inhibitor and an acute phase protein in the rat. Rat fibroblasts prepared from meninges or embryos and 3Y1-B clone 1-6 cells, a rat fibroblast cell line, secreted T-kininogen. Incubating these cells with 1 mM Bt2cAMP or a combination with 1 microM dexamethasone resulted in a marked increase in T-kininogen secretion, as well as in the incorporation of radioactive methionine into newly synthesized T-kininogen. Secretion of T-kininogen by meningeal fibroblasts was stimulated by forskolin, prostaglandin E2, bradykinin and cytokines, such as tumor necrosis factor alpha, interleukin-1 alpha (IL-1) and IL-6. Expression of T-kininogen mRNA was demonstrated in meningeal fibroblasts by Northern blot hybridization using T-kininogen cDNA as a probe, and the expression was stimulated by Bt2cAMP, prostaglandin E2, and the cytokines described above. In contrast, expression of T-kininogen mRNA in rat hepatocytes was not altered by Bt2cAMP, prostaglandin E2, tumor necrosis factor and IL-1, whereas it was greatly stimulated by IL-6, suggesting the differential regulation of T-kininogen gene expression in fibroblasts and hepatocytes. These results demonstrated for the first time, that rat fibroblasts express the T-kininogen gene, and that the expression is regulated by inflammatory mediators and cytokines.
Takano
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan.
Yokoyama
K
K
Yayama
K
K
Okamoto
H
H
D000262:Adenylyl Cyclases / Q000819:agonists; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression; D007704:Kininogens / Q000096:biosynthesis* / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008578:Meninges / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D016207:Cytokines; D007704:Kininogens; D012333:RNA, Messenger; D005576:Colforsin; D003994:Bucladesine; D003907:Dexamethasone; D000262:Adenylyl Cyclases; D015232:Dinoprostone