Angiotensin II differentially regulates interleukin-1-beta-inducible NO synthase (iNOS) and vascular cell adhesion molecule-1 (VCAM-1) expression: role of p38 MAPK.
Angiotensin II is implicated in pathophysiological processes associated with vascular injury and repair, which include regulating the expression of numerous NF-kappaB-dependent genes. The present study examined the effect of angiotensin II on interleukin-1beta-induced NF-kappaB activation and the subsequent expression of inducible NO synthase (iNOS) and vascular cell adhesion molecule-1 (VCAM-1) in cultured rat vascular smooth muscle cells. Neither NF-kappaB activation nor iNOS or VCAM-1 expression was induced in cells treated with angiotensin II alone. However, when added together with interleukin-1beta, angiotensin II, through activation of the AT(1) receptor, inhibited iNOS expression and enhanced VCAM-1 expression induced by the cytokine. The inhibitory effect of angiotensin II on iNOS expression was associated with a down-regulation of the sustained activation of extracellular signal-regulated kinase (ERK) and NF-kappaB by interleukin-1beta, whereas the effect on VCAM-1 was independent of ERK activation. The effect of angiotensin II on iNOS was abolished by inhibition of p38 mitogen-activated protein kinase (MAPK) with SB203580, but not by inhibition of PI3 kinase with wortmannin or stress-activated protein kinase/c-Jun NH(2)-terminal kinase (JNK) with JNK inhibitor II. Thus, angiotensin II, by a mechanism that requires the participation of p38 MAPK, differentially regulates the expression of NF-kappaB-dependent genes in response to interleukin-1beta stimulation by controlling the duration of activation of ERK and NF-kappaB.
Whitaker Cardiovascular Institute, Vascular Biology Unit, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. bjiang@bu.edu
Bingbing
B
Jiang
Shanqin
S
Xu
Xiuyun
X
Hou
David R
DR
Pimentel
Richard A
RA
Cohen
D000256:Adenoviridae / Q000235:genetics; D000730:Androstadienes / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015536:Down-Regulation; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D007527:Isoenzymes / Q000378:metabolism; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*; D000077191:Wortmannin; D048051:p38 Mitogen-Activated Protein Kinases
D000730:Androstadienes; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007375:Interleukin-1; D007527:Isoenzymes; D016328:NF-kappa B; D011725:Pyridines; D019010:Vascular Cell Adhesion Molecule-1; D000804:Angiotensin II; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D000077191:Wortmannin