Connective tissue growth factor (CTGF) is overexpressed in kidney diseases associated with extracellular matrix (ECM) accumulation. Angiotensin II (AngII) participates in renal fibrosis by the upregulation of growth factors, including CTGF, and ECM proteins, such as type IV collagen. During renal injury, AngII and the macrophage-produced cytokine interleukin-1- (IL-1-) may be present simultaneously in the glomerular environment. However, there are no studies about the interaction between AngII and IL-1- in renal fibrosis. For this reason, in cultured mesangial cells (MC), we have investigated whether IL-1- could regulate AngII-mediated collagen accumulation and the mechanisms underlying this process. In MC, CTGF is a downstream mediator of type IV collagen production induced by AngII. IL-1- did not increase the production of CTGF and type IV collagen, but significantly inhibited AngII-induced CTGF and type IV collagen overexpression. Moreover, IL-1- also inhibited type IV collagen upregulation caused by exogenous recombinant CTGF. Matrix metalloproteinase-9 (MMP-9) is the main enzyme involved in type IV collagen degradation. In MC, coincubation of IL-1- and AngII caused a synergistic increase on MMP-9 gene expression and activity, associated with type IV collagen inhibition. The described IL-1- effects were dependent on activation of ERK/MAPK, but independent p38-MAPK, JNK, PI3K/Akt and ROCK pathways. In summary, these data indicate that IL-1- inhibited AngII-mediated type IV collagen production, via CTGF down-regulation, and increased type IV collagen degradation, through MMP-9 upregulation. Our in vitro data show that the proinflammatory cytokine IL-1- abrogates AngII-induced CTGF production, describing antagonistic activities of pro-inflammatory cytokines on AngII actions.