Involvement of IL-6 and IL-6 receptor in fibrinogen synthesis in the liver of Triton WR-1339-induced hyperlipidemic rats.
To clarify the mechanisms by which Triton WR-1339 causes an elevation in the plasma fibrinogen level, we studied the time courses of hepatic mRNA expression for beta-chain fibrinogen, interleukin-6 (IL-6) and IL-6 receptor (R) by RT-PCR. After intravenous injection of Triton WR-1339 (150, 300 and 500 mg/kg) in Sprague-Dawley rats, the plasma level of fibrinogen and MCP-1 significantly and dose-relatedly increased from 12 to 24 hours (h). At 3 and 6 hours dose dependent increases were found in hepatic IL-6 and IL-6R mRNA expression with increases in the hepatic mRNA expression for beta-chain fibrinogen as the rate-limiting step in fibrinogen synthesis. These results suggest that the increase in the plasma fibrinogen level is followed by the enhancement of hepatic mRNA expression of beta-chain fibrinogen, IL-6 and IL-6R, that is, IL-6 and IL-6R may partly regulate the plasma fibrinogen level in Triton WR-1339-induced hyperlipidemic rats.
Ohta
Sumiko
S
Department of Pharmacology, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Okazaki
Masako
M
Maruyama
Mine
M
Oguchi
Katsuji
K
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005340:Fibrinogen / Q000096:biosynthesis*; D006949:Hyperlipidemias / Q000097:blood* / Q000139:chemically induced / Q000473:pathology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011092:Polyethylene Glycols; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D013501:Surface-Active Agents; D013997:Time Factors
C115499:BBeta fibrinogen; D015850:Interleukin-6; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; D005340:Fibrinogen; C016811:tyloxapol