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 α (TNFα), have been reported to play a role in various heart diseases and OPC-8212, a quinolinone derivative, has been demonstrated to reduce TNFα 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 TNFα, we examined the effects of OPC-8212 on the expression of type III collagen mRNA [α1(III)] in cultured neonatal rat cardiac fibroblasts. We also measured the concentration of TNFα and transforming growth factor β (TGFβ) in the cultured medium. Northern blot analysis revealed that LPS reduced the expression of α1(III) mRNA, and OPC-8212 counteracted this reduction (on average 25% above the reduced level by LPS stimulation). LPS enhanced the TNFα concentration in the medium, and OPC-8212 inhibited this enhancement. LPS increased the TGF-β1 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 TNFα.
2001 by the Japanese Heart Journal