Induction of IkappaB: atrial natriuretic peptide as a regulator of the NF-kappaB pathway.
Atrial natriuretic peptide (ANP) was shown to possess anti-inflammatory potential due to its potency to inhibit the production of inflammatory mediators, such as TNF-alpha. The aim of this study was to determine potential effects of ANP on endothelial cells targeted by TNF-alpha. HUVEC were treated with TNF-alpha and expression of adhesion molecules was investigated by FACS and RT-PCR. Pre-treatment of cells with ANP (30min) significantly reduced TNF-alpha-induced cell surface protein and mRNA expression of E-selectin and ICAM-1, whereas it did not influence VCAM-1. ANP reduced TNF-alpha-induced NF-kappaB activity, which was paralleled by a decreased translocation of p65 to nuclei. ANP did not alter TNF-alpha-induced phosphorylation and degradation of IkappaB-alpha, but attenuated degradation of IkappaB-epsilon. Moreover, ANP leads to a transcriptional induction of IkappaB-alpha. The induction of IkappaB by ANP is suggested as a novel mechanism for regulating inflammatory signalling in endothelial cells, leading to reduced TNF-alpha-induced expression of adhesion molecules.
Department of Pharmacy, Center of Drug Research, University of Munich, Butenandtstrasse 5-13, 81377 Munich, Germany. alexandra.kiemer@cup.uni-muenchen.de
Alexandra K
AK
Kiemer
Nina C
NC
Weber
Angelika M
AM
Vollmar
D021581:Active Transport, Cell Nucleus; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D019040:E-Selectin; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C105627:NFKBIE protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP