Abstract
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-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.
MeSH terms
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Adipocytes / drug effects*
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Adipocytes / metabolism
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Adult
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Angiotensin II / antagonists & inhibitors
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Angiotensin II / pharmacology*
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Angiotensin II Type 1 Receptor Blockers / pharmacology*
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Angiotensin II Type 2 Receptor Blockers
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Benzimidazoles / pharmacology
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Biphenyl Compounds
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Cells, Cultured / drug effects
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Cells, Cultured / metabolism
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Electrophoretic Mobility Shift Assay
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Female
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Humans
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Imidazoles / pharmacology
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Inflammation
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Interleukin-6 / biosynthesis
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Interleukin-6 / genetics
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Interleukin-6 / metabolism*
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Interleukin-8 / biosynthesis
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Interleukin-8 / genetics
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Interleukin-8 / metabolism*
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism*
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Nitriles / pharmacology
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Phosphorylation / drug effects
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Protein Processing, Post-Translational / drug effects
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Protein Transport / drug effects
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Pyridines / pharmacology
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RNA, Messenger / biosynthesis
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Receptor, Angiotensin, Type 1 / drug effects*
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Receptor, Angiotensin, Type 1 / physiology
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Sulfones / pharmacology
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Tetrazoles / pharmacology
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Transcription Factor RelA
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Transcriptional Activation / drug effects
Substances
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3-(4-methylphenylsulfonyl)-2-propenenitrile
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Angiotensin II Type 1 Receptor Blockers
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Angiotensin II Type 2 Receptor Blockers
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Benzimidazoles
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Biphenyl Compounds
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Imidazoles
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Interleukin-6
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Interleukin-8
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NF-kappa B
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Nitriles
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Pyridines
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RNA, Messenger
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Receptor, Angiotensin, Type 1
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Sulfones
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Tetrazoles
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Transcription Factor RelA
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Angiotensin II
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PD 123319
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candesartan