Insulin suppresses LPS-induced iNOS and COX-2 expression and NF-kappa B activation in alveolar macrophages
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
---|---|
Data(s) |
20/10/2012
20/10/2012
2008
|
Resumo |
The development of septic shock is a common and frequently lethal consequence of gram-negative infection. Mediators released by lung macrophages activated by bacterial products such as lipopolysaccharide (LPS) contribute to shock symptoms. We have shown that insulin downregulates LPS-induced TNF production by alveolar macrophages (AMs). In the present study, we investigated the effect of insulin on the LPS-induced production of nitric oxide (NO) and prostaglandin (PG)-E(2), on the expression of inducible nitric oxide synthase ( iNOS) and cyclooxygenase (COX)-2, and on nuclear factor kappa B (NF-kappa B) activation in AMs. Resident AMs from male Wistar rats were stimulated with LPS (100 ng/mL) for 30 minutes. Insulin (1 mU/mL) was added 10 min before LPS. Enzymes expression, NF-kappa B p65 activation and inhibitor of kappa B (I-kappa B) a phosphorylation were assessed by immunobloting; NO by Griess reaction and PGE(2) by enzyme immunoassay (EIA). LPS induced in AMs the expression of iNOS and COX-2 proteins and production of NO and PGE(2), and, in parallel, NF-kappa B p65 activation and cytoplasmic I-kappa B alpha phosphorylation. Administration of insulin before LPS suppressed the expression of iNOS and COX-2, of NO and PGE(2) production and Nuclear NF-kappa B p65 activation. Insulin also prevented cytoplasmic I-kappa Ba phosphorylation. These results show that in AMs stimulated by LPS, insulin prevents nuclear translocation of NF-kappa B, possibly by blocking I-kappa Ba degradation, and supresses the production of NO and PGE(2), two molecules that contribute to septic shock. Copyright (C) 2008 S. Karger AG, Basel. |
Identificador |
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, v.22, n.1/Abr, p.279-286, 2008 1015-8987 http://producao.usp.br/handle/BDPI/28243 10.1159/000149806 |
Idioma(s) |
eng |
Publicador |
KARGER |
Relação |
Cellular Physiology and Biochemistry |
Direitos |
restrictedAccess Copyright KARGER |
Palavras-Chave | #insulin #LPS #macrophages #NO #iNOS #PGE(2) #COX-2 #NF-kappa B #I kappa B alpha #PROSTAGLANDIN-ENDOPEROXIDE SYNTHASE-2 #NITRIC-OXIDE SYNTHASE #MONONUCLEAR-CELLS #GENE #INFLAMMATION #INDUCTION #PROTEIN #ALPHA #THERAPY #SEPSIS #Cell Biology #Physiology |
Tipo |
article original article publishedVersion |