Regulation of murine protein C gene expression in vivo: effects of tumor necrosis factor-alpha, interleukin-1, and transforming growth factor-beta.
Protein C is a precursor of the anticoagulant serine protease, activated protein C, which inhibits coagulation factors Va and VIIIa. Although the liver appears to be the primary site of protein C synthesis, we previously demonstrated that the kidney and male reproductive organs also expressed abundant protein C mRNA in the mouse. In the present study, we further investigated the effects of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and transforming growth factor-beta (TGF-beta) on the expression of protein C mRNA in the principal producing organs, i.e., the liver, kidney, and testis. Both quantitative reverse transcription-PCR assay and in situ hybridization analysis revealed that TNF-alpha decreased protein C mRNA expression in the liver, kidney, and testis. IL-1 also down-regulated protein C mRNA expression in the liver and testis, but not in the kidney. In contrast, TGF-beta unchanged the expression level of protein C mRNA in these three organs. These observations suggest that TNF-alpha and IL-1 may contribute to an increase in the procoagulant potential by downregulation of protein C synthesis in the tissues during inflammatory processes.
Yamamoto
K
K
First Department of Internal Medicine, Nagoya University School of Medicine, Showa, Japan. kojiy@tsuru.med.nagoya-u.ac.jp
Shimokawa
T
T
Kojima
T
T
Loskutoff
D J
DJ
Saito
H
H
D000818:Animals; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects*; D017403:In Situ Hybridization; D007249:Inflammation / Q000235:genetics; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009928:Organ Specificity; D011486:Protein C / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D011486:Protein C; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha