on May 6, 2004
Published online before print May 6, 2004, doi: 10.1161/01.ATV.0000131266.38312.2e
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Submitted on March 23, 2004
Accepted on April 12, 2004
Angiotensin II Stimulates the Release of Interleukin-6 and Interleukin-8 From Cultured Human Adipocytes by Activation of NF-
B
Thomas Skurk *;
From Else Kröner Fresenius Zentrum für Ernährungsmedizin der TU München, Freising-Weihenstephan, Germany.
* To whom correspondence should be addressed. E-mail: skurk{at}wzw.tum.de.
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.
Methods and 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-
B-blocker Bay 11 to 7082 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-B and an increased translocation of NF-B to the nucleus.
Conclusion--Ang II stimulates IL-6 and IL-8 production and release from human adipocytes by a NF-B-dependent pathway. This proinflammatory action of Ang II seems to be mediated by the AT1 and less by the AT2 receptor subtype.
Key words: cytokines • adipocytes • angiotensin • AT1 receptor • NF-
B
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