Interleukin-1 Increases Fibronectin Production by Cultured Rat Cardiac Fibroblasts

Objectives: There is evidence of monocyte/macrophage infiltration and increased interleukin (IL)-1 expression, along with increased extracellular matrix (ECM) and fibrosis in the myocardial interstitium, during the course of parasitic, viral and idiopathic myocarditis. The aim of this study was to determine the effect of human and rat IL-1 on the production of fibronectin (FN) by rat cardiac fibroblast cultures.

Methods: To test the role of IL-1 in the production of ECM, we determined the FN content in supernatants of rat myocardial fibroblast cultures incubated for 72 h with different doses of human recombinant IL-1beta or with supernatants from lipopolysaccharide (LPS)-stimulated rat macrophage cultures. The content of soluble FN was determined by ELISA. In addition, IL-1beta transcription was also investigated in controls and human recombinant IL-1beta-treated fibroblast cultures.

Results: There was a significant, dose-dependent FN-stimulatory effect of recombinant human IL-1beta and LPS-stimulated macrophage-conditioned medium when they were used to stimulate fibroblast cultures. The stimulatory effect on FN production was found to be diminished after treatment of macrophage supernatants with an antibody against rat IL-1. Increased transcription of IL-1beta was found in human recombinant IL-1beta-treated cardiac fibroblasts.

Conclusion: Our data suggest that the FN-stimulatory effect of IL-1 on cardiac fibroblasts could be responsible, in part, for interstitial ECM accumulation during the course of myocarditis.