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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1199.)
© 2004 American Heart Association, Inc.

Vascular Biology

Angiotensin II Stimulates the Release of Interleukin-6 and Interleukin-8 From Cultured Human Adipocytes by Activation of NF-B

Thomas Skurk; Vanessa van Harmelen; Hans Hauner

From Else Kröner Fresenius Zentrum für Ernährungsmedizin der TU München, Freising-Weihenstephan, Germany.

Correspondence to Dr Thomas Skurk, Else Kröner Fresenius Zentrum für Ernährungsmedizin der TU München, Hochfeldweg 1, 85350 Freising-Weihenstephan, Germany. 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 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-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.

The effect of angiotensin (Ang) II on the production of IL-6 and IL-8 in in vitro differentiated human adipocytes was studied. Ang II-stimulated IL-6 and IL-8 production by a NF-B-dependent pathway. This proinflammatory action of Ang II was mediated by the AT₁ and less by the AT₂ receptor.

Key Words: cytokines • adipocytes • angiotensin • AT₁ receptor • NF-B

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