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This Article Full Text Full Text (PDF) All Versions of this Article: 294/1/F149    most recent 00129.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sánchez-López, E. Articles by Ruiz-Ortega, M. Search for Related Content PubMed PubMed Citation Articles by Sánchez-López, E. Articles by Ruiz-Ortega, M.

Inhibitory effect of interleukin-1β on angiotensin II-induced connective tissue growth factor and type IV collagen production in cultured mesangial cells

¹Cellular Biology in Renal Diseases Laboratory and ²Renal Unit, Fundación Jiménez Díaz, Universidad Autónoma Madrid, Madrid, Spain

Submitted 19 March 2007 ; accepted in final form 26 October 2007

Connective tissue growth factor (CTGF) is overexpressed in kidney diseases associated with extracellular matrix accumulation. Angiotensin II (ANG II) participates in renal fibrosis by the upregulation of growth factors, including CTGF, and extracellular matrix proteins, such as type IV collagen. During renal injury, ANG II and the macrophage-produced cytokine interleukin-1β (IL-1β) may be present simultaneously in the glomerular environment. However, there are no studies about the interaction between ANG II and IL-1β in renal fibrosis. For this reason, in cultured mesangial cells (MC), we investigated whether IL-1β could regulate ANG II-mediated collagen accumulation and the mechanisms underlying this process. In MC, CTGF is a downstream mediator of type IV collagen production induced by ANG II. IL-1β did not increase the production of CTGF and type IV collagen but significantly inhibited ANG II-induced CTGF and type IV collagen overexpression. Moreover, IL-1β 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-1β and ANG II caused a synergistic increase in MMP-9 gene expression and activity, associated with type IV collagen inhibition. The described IL-1β effects were dependent on activation of ERK/MAPK but independent p38-MAPK, JNK, phosphatidylinositol 3-kinase/Akt, and Rho-associated kinase pathways. In summary, these data indicate that IL-1β inhibited ANG II-mediated type IV collagen production, via CTGF downregulation, and increased type IV collagen degradation, through MMP-9 upregulation. Our in vitro data show that the proinflammatory cytokine IL-1β abrogates ANG II-induced CTGF production, describing antagonistic activities of proinflammatory cytokines on ANG II actions.

transforming growth factor-β; extracellular-regulated kinase; metalloproteinases