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 cytok ines, including tumor necrosis factor alpha (TNF alpha), have been reported to play a role in various heart diseases and OPC-8212, a quinolinone deriv ative, has been demonstrated to reduce TNF alpha production. No studies hav e examined the effects of OPC-8212 on collagen metabolism in connection wit h inflammatory cytokine and growth factors. Using lipopolysaccharides as a tool to enhance TNF alpha, we examined the effects of OPC-8212 on the expre ssion of type III collagen mRNA [alpha1(III)] in cultured neonatal rat card iac fibroblasts. We also measured the concentration of TNF alpha and transf orming growth factor beta (TGF beta) 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 leve l by LPS stimulation). LPS enhanced the TNF alpha concentration in the medi um, and OPC-8212 inhibited this enhancement. LPS increased the TGF-beta1 co ncentration in the cultured medium, while OPC-8212 did not affect this incr ease. In summary, OPC-8212 counteracted the reduction in type III collagen mRNA expression by LPS accompanied by suppression of the increase in TNF al pha.