Angiotensin II activates the proinflammatory transcription factor nuclear factor-kappaB in human monocytes.
The renin-angiotensin system may contribute to the pathogenesis of atherosclerosis. A common feature of all stages of atherosclerosis is inflammation of the vessel wall. The transcription factor nuclear factor-kappaB (NF-kappaB) participates in most signaling pathways involved in inflammation. This study therefore examined the effect of angiotensin (ANG) II on NF-kappaB activation in monocytic cells, a major cellular component of human atheroma, by electrophoretic mobility shift assay. ANG II, like TNFalpha, caused rapid activation of NF-kappaB in human mononuclear cells isolated from peripheral blood by Ficoll density gradient. This ANG II effect was blocked by the angiotensin AT1 receptor antagonist losartan. Specificity of ANG II-induced NF-kappaB activation was ascertained by supershift and competition experiments. Moreover, ANG II stimulated NF-kappaB activation in human monocytes, but not in lymphocytes from the same preparation. Together, the data demonstrate the ability of the vasoactive peptide ANG II to activate inflammatory pathways in human monocytes.
Kranzhöfer
R
R
Department of Cardiology, University of Heidelberg, Heidelberg, Germany. rober_kranzhoefer@med.uni-heidelberg.de
Browatzki
M
M
Schmidt
J
J
Kübler
W
W
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D001161:Arteriosclerosis / Q000473:pathology; D001667:Binding, Competitive; D002469:Cell Separation; D016384:Consensus Sequence; D006801:Humans; D007249:Inflammation; D019808:Losartan / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology; D013997:Time Factors; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009841:Oligonucleotides; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D019808:Losartan