Endotoxin-induced renal inflammatory response - Oncostatin M as a major mediator of suppressed renin expression

The systemic response to endotoxin is characterized by hypotension and seve re reductions in blood pressure, leading to cardiovascular collapse that ca n accompany septicemia. The renin/ansotensin system would normally be expec ted to respond to hypotensive challenge; however, inflammation appears to m odify this response. This study identifies a strong acute phase response of the kidney that is characterized by enhanced expression of serum amyloid A , haptoglobin and tissue inhibitor for metalloproteinase-1 and a reduced ex pression of renin, Equivalent regulatory effects were observed for the immo rtalized As4.1 kidney cell line that models certain features of juxtaglomer ular cells. Oncostatin M, a known endotoxin-responsive proinflammatory cyto kine, proved to be an effective inhibitor of renin gene expression. Suppres sion by oncostatin M involves activated STAT5 and requires an inhibitory el ement in the renin promoter that functions separately from cell type-specif ic enhancer elements. The renal acute phase reaction, unlike the liver acut e phase reaction, is more strongly dependent on locally produced inflammato ry factors.