期刊
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
卷 69, 期 4, 页码 329-336出版社
WILEY-BLACKWELL PUBLISHING, INC
DOI: 10.1111/j.1365-3083.2008.02224.x
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资金
- Arthritis Research Campaign UK
- MRC [G7811974]
- Wellcome Trust [072643/Z/03/Z]
- EUFP6 Integrated Project [LSHM-CT-2003-503041]
- NIHR Biomedical Research Centre
- BHF intermediate fellowship [FS/06/001]
- MRC [G7811974] Funding Source: UKRI
- Medical Research Council [G7811974] Funding Source: researchfish
Obesity is regarded as a pro-inflammatory state. It is associated with low circulating levels of the adipokine, adiponectin, which is considered to be an anti-inflammatory. However, adiponectin knockout mice do not consistently demonstrate pro-inflammatory phenotypes, suggesting more complexity in the in vivo immunomodulatory effects of adiponectin than originally anticipated. Moreover, adiponectin exerts pro-inflammatory effects in some experimental systems. This contradiction has been resolved by hypothesizing that adiponectin induces tolerance to inflammatory stimuli, notably Toll-like receptor (TLR) ligands. We noticed that this effect resembled lipopolysaccharide (LPS) tolerance and therefore tested adiponectin from a variety of sources for LPS contamination. All adiponectin tested carried low levels of LPS in the range of 1-30 pg/mu g of adiponectin, sufficient to produce final LPS concentrations in the pg/ml range under experimental conditions. We found that induction of tolerance to TLR ligands by adiponectin in human monocyte-derived macrophages could be reproduced by such LPS concentrations. Moreover, the LPS antagonist, polymixin B, substantially inhibited induction of tolerance by adiponectin. Furthermore, polymixin B and a naturally occurring antagonist LPS were able to partially attenuate induction of tumour necrosis factor-alpha and interleukin-6 in human monocyte-derived macrophages by adiponectin. Polymixin B also inhibited nuclear factor-kappa B and mitogen-activated protein kinase signalling elicited by adiponectin. We therefore propose that some of adiponectin's immunomodulatory effects, in particular, its TLR-tolerising actions in human monocyte-derived macrophages, may be confounded by induction of tolerance by contaminating LPS.
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