title: Endotoxin-induced renal inflammatory response. Oncostatin M as a major mediator of suppressed renin expression.
abstract: The systemic response to endotoxin is characterized by hypotension and severe reductions in blood pressure, leading to cardiovascular collapse that can accompany septicemia. The renin/angiotensin system would normally be expected to respond to hypotensive challenge; however, inflammation appears to modify 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 expression of renin. Equivalent regulatory effects were observed for the immortalized As4.1 kidney cell line that models certain features of juxtaglomerular cells. Oncostatin M, a known endotoxin-responsive proinflammatory cytokine, proved to be an effective inhibitor of renin gene expression. Suppression by oncostatin M involves activated STAT5 and requires an inhibitory element in the renin promoter that functions separately from cell type-specific enhancer elements. The renal acute phase reaction, unlike the liver acute phase reaction, is more strongly dependent on locally produced inflammatory factors.
authors.affiliation: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. Heinz.Baumann@sc3101.med.buffalo.edu
authors.forename: H
authors.initials: H
authors.lastname: Baumann
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: C D
authors.initials: CD
authors.lastname: Richards
authors.forename: C A
authors.initials: CA
authors.lastname: Jones
authors.forename: T A
authors.initials: TA
authors.lastname: Black
authors.forename: K W
authors.initials: KW
authors.lastname: Gross
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008894:Milk Proteins; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism*; D012083:Renin / Q000378:metabolism*; D012084:Renin-Angiotensin System; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D004731:Endotoxins; D008894:Milk Proteins; C508352:Osm protein, mouse; D010455:Peptides; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D053683:Oncostatin M; D012083:Renin