Macrophage-stimulated cardiac-fibroblast production of IL-6 induced TGF-β1 production and Smad3 phosphorylation in cardiac fibroblasts, which promoted the differentiation of cardiac fibroblasts into myofibroblasts in vivo and in vitro. Finally, IL-6 deficiency reduced Ang II-induced cardiac inflammation and fibrosis. The gene discussed is SMAD3; the disease is inflammation.