MAP kinase phosphatase 2 regulates macrophage-adipocyte interaction.

Huipeng Jiao,Peng Tang,Yongliang Zhang,Haiyan Xu

doi:10.1371/journal.pone.0120755

Huipeng Jiao, Peng Tang + Show 2 more

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https://doi.org/10.1371/journal.pone.0120755

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Journal: PloS one	Publication Date: Mar 27, 2015
Citations: 9	License type: CC BY 4.0

Affiliation: National University of Singapore

Abstract

ObjectiveInflammation is critical for the development of obesity-associated metabolic disorders. This study aims to investigate the role of mitogen-activated protein kinase phosphatase 2 (MKP-2) in inflammation during macrophage-adipocyte interaction.MethodsWhite adipose tissues (WAT) from mice either on a high-fat diet (HFD) or normal chow (NC) were isolated to examine the expression of MKP-2. Murine macrophage cell line RAW264.7 stably expressing MKP-2 was used to study the regulation of MKP-2 in macrophages in response to saturated free fatty acid (FFA) and its role in macrophage M1/M2 activation. Macrophage-adipocyte co-culture system was employed to investigate the role of MKP-2 in regulating inflammation during adipocyte-macrophage interaction. c-Jun N-terminal kinase (JNK)- and p38-specific inhibitors were used to examine the mechanisms by which MKP-2 regulates macrophage activation and macrophage-adipocytes interaction.ResultsHFD changed the expression of MKP-2 in WAT, and MKP-2 was highly expressed in the stromal vascular cells (SVCs). MKP-2 inhibited the production of proinflammatory cytokines in response to FFA stimulation in macrophages. MKP-2 inhibited macrophage M1 activation through JNK and p38. In addition, overexpression of MKP-2 in macrophages suppressed inflammation during macrophage-adipocyte interaction.ConclusionMKP-2 is a negative regulator of macrophage M1 activation through JNK and p38 and inhibits inflammation during macrophage-adipocyte interaction.

Highlights

Obesity—a rapidly emerging major public health issue worldwide—is associated with an increased risk of insulin resistance and type 2 diabetes (T2D) [1]
high-fat diet (HFD) changed the expression of MKP-2 in White adipose tissues (WAT), and MKP-2 was highly expressed in the stromal vascular cells (SVCs)
MKP-2 is a negative regulator of macrophage M1 activation through Jun N-terminal kinase (JNK) and p38 and inhibits inflammation during macrophage-adipocyte interaction

Summary

Introduction

Obesity—a rapidly emerging major public health issue worldwide—is associated with an increased risk of insulin resistance and type 2 diabetes (T2D) [1]. Expansion of adipose tissue in obesity leads to increased macrophage infiltration and inflammation with enhanced production of proinflammatory cytokines such as tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6). This is accompanied by an increased release of free fatty acids (FFAs) and dysregulated secretion of adipocyte- and macrophage-derived factors, including leptin, adiponectin, and resistin [3,4]. These mediators (collectively known as adipokines) can act in a paracrine or autocrine fashion to further exacerbate adipose tissue inflammation and reduce insulin sensitivity [5]. M1 macrophage activation can be induced in vitro by proinflammatory mediators such as interferon (IFN)-γ and lipopolysaccharides (LPS) [8], while M2 macrophages can be induced by exposure to IL-4 and IL-13 [7,9]

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Conclusion