Angiotensin II stimulates the release of interleukin-6 and interleukin-8 from cultured human adipocytes by activation of NF-kappaB.
OBJECTIVE
Several proinflammatory cytokines including IL-6 and IL-8 are produced by human adipocytes, but it is still unclear how this process is regulated. Angiotensin (Ang) II, which is also produced by adipocytes, might play a role as a regulator. In the present study, we investigated the effect of Ang II on the production of IL-6 and IL-8 in in vitro differentiated human adipocytes.


RESULTS
Isolation of preadipocytes and differentiation of these cells into adipocytes, Real-time quantitative reverse-transcriptase polymerase chain reaction, Western-blot, enzyme-linked immunosorbent assay, and electromobility shift assay. Ang II-stimulated IL-6 and IL-8 mRNA expression and protein release in a time- and concentration-dependent way. This action of Ang II was completely blocked by the NF-kappaB-blocker Bay 117082 and the AT1 blocker candesartan, but only partially by the AT2-blocker PD 123 319. Incubation of adipocytes with Ang II resulted in an increased phosphorylation of the p65 subunit of NF-kappaB and an increased translocation of NF-kappaB to the nucleus.


CONCLUSIONS
Ang II stimulates IL-6 and IL-8 production and release from human adipocytes by a NF-kappaB-dependent pathway. This proinflammatory action of Ang II seems to be mediated by the AT1 and less by the AT2 receptor subtype.
Skurk
Thomas
T
Else Kröner Fresenius Zentrum für Ernährungsmedizin der TU München, Hochfeldweg 1, 85350 Freising-Weihenstephan, Germany. skurk@wzw.tum.de
van Harmelen
Vanessa
V
Hauner
Hans
H
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D057912:Angiotensin II Type 2 Receptor Blockers; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000502:physiology; D013450:Sulfones / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology; D051996:Transcription Factor RelA; D015533:Transcriptional Activation / Q000187:drug effects
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007093:Imidazoles; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D009570:Nitriles; D011725:Pyridines; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D013450:Sulfones; D013777:Tetrazoles; D051996:Transcription Factor RelA; D000804:Angiotensin II; C073402:PD 123319; C081643:candesartan