OPC-8212, a quinoline derivative, counteracts the reduction in type III collagen mRNA due to lipopolysaccharides in cultured rat cardiac fibroblasts.
Fibrillar collagen plays an essential role in ventricular remodeling, which is a major prognostic factor in various heart diseases. Inflammatory cytokines, including tumor necrosis factor alpha (TNFalpha), have been reported to play a role in various heart diseases and OPC-8212, a quinolinone derivative, has been demonstrated to reduce TNFalpha production. No studies have examined the effects of OPC-8212 on collagen metabolism in connection with inflammatory cytokine and growth factors. Using lipopolysaccharides as a tool to enhance TNFalpha, we examined the effects of OPC-8212 on the expression of type III collagen mRNA [alpha1(III)] in cultured neonatal rat cardiac fibroblasts. We also measured the concentration of TNFalpha and transforming growth factor beta (TGFbeta) in the cultured medium. Northern blot analysis revealed that LPS reduced the expression of alpha1(III) mRNA, and OPC-8212 counteracted this reduction (on average 25% above the reduced level by LPS stimulation). LPS enhanced the TNFalpha concentration in the medium, and OPC-8212 inhibited this enhancement. LPS increased the TGF-beta1 concentration in the cultured medium, while OPC-8212 did not affect this increase. In summary, OPC-8212 counteracted the reduction in type III collagen mRNA expression by LPS accompanied by suppression of the increase in TNFalpha.
Sano
I
I
Department of Internal Medicine I, Faculty of Medicine, Okayama, Japan.
Kusachi
S
S
Murakami
T
T
Ninomiya
Y
Y
Oka
T
T
Nunoyama
H
H
Kumashiro
H
H
Iwabu
A
A
Ueta
J
J
Tsuji
T
T
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003094:Collagen / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism*; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D011719:Pyrazines; D011804:Quinolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D016212:Transforming Growth Factor beta / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D002316:Cardiotonic Agents; D008070:Lipopolysaccharides; D011719:Pyrazines; D011804:Quinolines; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C041667:vesnarinone; D003094:Collagen