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Leptin enhances the secretion of interleukin (IL)-18, but not IL-1B, from human monocytes via activation of caspase-1.

Jitprasertwong, P, Jaedicke, Katrin, Nile, CJ, Preshaw, PM and Taylor, JJ (2013) Leptin enhances the secretion of interleukin (IL)-18, but not IL-1B, from human monocytes via activation of caspase-1. Cytokine, 65 (2). pp. 222-230. ISSN 1043-4666

Item Type: Article

Abstract

Circulating levels of leptin are elevated in type-2 diabetes mellitus (T2DM) and leptin plays a role in immune responses. Elevated circulating IL-18 levels are associated with clinical complications of T2DM. IL-18 regulates cytokine secretion and the function of a number of immune cells including T-cells, neutrophils and macrophages and as such has a key role in immunity and inflammation. Pro-inflammatory monocytes exhibiting elevated cytokine secretion are closely associated with inflammation in T2DM, however, little is known about the role of leptin in modifying monocyte IL-18 secretion. We therefore aimed to investigate the effect of leptin on IL-18 secretion by monocytes. We report herein that leptin increases IL-18 secretion in THP-1 and primary human monocytes but has no effect on IL-18 mRNA. Leptin and LPS signalling in monocytes occurs by overlapping but distinct pathways. Thus, in contrast to a strong stimulation by LPS, leptin has no effect on IL-1β mRNA levels or IL-1β secretion. In addition, LPS stimulates the secretion of IL-6 but leptin did not whereas both treatments up regulate IL-8 secretion from the same cells. Although leptin (and LPS) has a synergistic effect with exogenous ATP on IL-18 secretion in both THP-1 and primary monocytes, experiments involving ATP assays and pharmacological inhibition of ATP signalling failed to provide any evidence that endogenous ATP secreted by leptin-stimulated monocytes was responsible for enhancement of monocyte IL-18 secretion by leptin. Analysis of the action of caspase-1 revealed that leptin up regulates caspase-1 activity and the effect of leptin on IL-18 release is prevented by caspase-1 inhibitor (Ac-YVAD-cmk). These data suggest that leptin activates IL-18 processing rather than IL-18 transcription. In conclusion, leptin enhances IL-18 secretion via modulation of the caspase-1 inflammasome function and acts synergistically with ATP in this regard. This process may contribute to aberrant immune responses in T2DM and other conditions of hyperleptinemia.

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More Information

Depositing User: Katrin Jaedicke

Identifiers

Item ID: 9356
Identification Number: https://doi.org/10.1016/j.cyto.2013.10.008
ISSN: 1043-4666
URI: http://sure.sunderland.ac.uk/id/eprint/9356
Official URL: https://www.sciencedirect.com/science/article/pii/...

Users with ORCIDS

ORCID for Katrin Jaedicke: ORCID iD orcid.org/0000-0002-7389-5816

Catalogue record

Date Deposited: 16 May 2018 12:27
Last Modified: 18 Dec 2019 16:06

Contributors

Author: Katrin Jaedicke ORCID iD
Author: P Jitprasertwong
Author: CJ Nile
Author: PM Preshaw
Author: JJ Taylor

University Divisions

Faculty of Health Sciences and Wellbeing
Faculty of Health Sciences and Wellbeing > School of Nursing and Health Sciences

Subjects

Sciences > Health Sciences

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