M. Takano et al., RAT FIBROBLASTS SYNTHESIZE T-KININOGEN IN RESPONSE TO CYCLIC-AMP, PROSTAGLANDIN E(2) AND CYTOKINES, Biochimica et biophysica acta. Molecular cell research, 1268(1), 1995, pp. 107-114
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 cel
ls, a rat fibroblast cell line, secreted T-kininogen. Incubating these
cells with 1 mM Bt(2)cAMP or a combination with 1 mu M dexamethasone
resulted in a marked increase in T-kininogen secretion, as well as in
the incorporation of radioactive methionine into newly synthesized T-k
ininogen. Secretion of T kinino en by meningeal fibroblasts was stimul
ated by forskolin, prostaglandin E(2), bradykinin and cytokines, such
as tumor necrosis factor alpha, interleukin-1 alpha (IL-1) and IL-6. E
xpression of T-kininogen mRNA was demonstrated in meningeal fibroblast
s by Northern blot hybridization using T-kininogen cDNA as a probe, an
d the expression was stimulated by Bt(2)cAMP, prostaglandin E(2), and
the cytokines described above. In contrast, expression of T-kininogen
mRNA in rat hepatocytes was not altered by Bt(2)cAMP, prostaglandin E(
2), tumor necrosis factor and DL-l, whereas it was greatly stimulated
by IL-6, suggesting the differential regulation of T-kininogen gene ex
pression in fibroblasts and hepatocytes, These results demonstrated fo
r the first time, that rat fibroblasts express the T-kininogen gene, a
nd that the expression is regulated by inflammatory mediators and cyto
kines.