Induction of TLR tolerance in human macrophages by adiponectin: does LPS play a role?

Turner, JJ, Smolinska, M J, Sacre, S M and Foxwell, B M J (2009) Induction of TLR tolerance in human macrophages by adiponectin: does LPS play a role? Scandinavian Journal of Immunology, 69 (4). pp. 329-336. ISSN 0300-9475

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Abstract

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/microg 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-kappaB 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.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Rhiannon Harvey
Date Deposited: 20 Apr 2011 12:38
Last Modified: 21 Apr 2020 17:48
URI: https://ueaeprints.uea.ac.uk/id/eprint/29731
DOI: 10.1111/j.1365-3083.2008.02224.x

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