Journal Article

Adiponectin suppression of late inflammatory mediator, HMGB1-induced cytokine expression in RAW264 macrophage cells

Mohamed Elfeky, Takeshi Yoneshiro, Yuko Okamatsu-Ogura and Kazuhiro Kimura

in The Journal of Biochemistry

Volume 163, issue 2, pages 143-153
Published in print February 2018 | ISSN: 0021-924X
Published online October 2017 | e-ISSN: 1756-2651 | DOI: https://dx.doi.org/10.1093/jb/mvx069
Adiponectin suppression of late inflammatory mediator, HMGB1-induced cytokine expression in RAW264 macrophage cells

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Abstract

High-mobility group protein B1 (HMGB1) is a late inflammatory mediator released from inflammatory cells when stimulated, resulting in exaggerating septic symptoms. We recently demonstrated that full-length adiponectin, a potent anti-inflammatory adipokine, inhibits lipopolysaccharide-induced HMGB1 release. However, the effects of adiponectin on HMGB1-induced exaggerating signals currently remain unknown. This study aimed to investigate the effects of adiponectin on the pro-inflammatory function of HMGB1 in RAW264 macrophage cells. The treatment of RAW264 cells with HMGB1 significantly up-regulated the mRNA expression of tumour necrosis factor-α, interleukin-1β and C-X-C motif chemokine 10. HMGB1-induced cytokine expression was markedly suppressed by a toll-like receptor 4 (TLR4) antagonist and slightly suppressed by an antagonist of the receptor for advanced glycation end products. A prior treatment with full-length or globular adiponectin dose-dependently suppressed all types of HMGB1-induced cytokine expression, and this suppression was abolished by compound C, an AMPK inhibitor, but not by the haem oxygenase (HO)-1 inhibitor, zinc protoporphyrin IX. Both forms of adiponectin also reduced the mRNA expression of TLR4. These results suggest that full-length and globular adiponectin suppress HMGB1-induced cytokine expression through an AMPK-mediated HO-1-independent pathway.

Keywords: adiponectin; high-mobility group protein B1; inflammation; macrophages; toll-like receptor 4

Journal Article.  5939 words.  Illustrated.

Subjects: Cell Biology ; Biotechnology ; Biochemistry ; Molecular and Cell Biology

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