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 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.
Baumann
H
H
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. Heinz.Baumann@sc3101.med.buffalo.edu
Wang
Y
Y
Richards
C D
CD
Jones
C A
CA
Black
T A
TA
Gross
K W
KW
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
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