MAP kinase phosphatase 2 regulates macrophage-adipocyte interaction.

Abstract

OBJECTIVE:

Inflammation 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.

METHODS:

White 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.

RESULTS:

HFD 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.

CONCLUSION:

MKP-2 is a negative regulator of macrophage M1 activation through JNK and p38 and inhibits inflammation during macrophage-adipocyte interaction.

• Authors: Huipeng Jiao, Peng Tang, Yongliang Zhang
• Journal: PloS one (PLoS One) Vol. 10 Issue 3 Pg. e0120755 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25816341 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• RNA, Messenger
• JNK Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• MKP2 protein, mouse
• Protein Tyrosine Phosphatases

Topics

• Adipocytes (cytology, metabolism)
• Animals
• Blotting, Western
• Cells, Cultured
• Coculture Techniques
• Cytokines (genetics, metabolism)
• Diet, High-Fat
• Enzyme Activation
• JNK Mitogen-Activated Protein Kinases (genetics, metabolism)
• MAP Kinase Signaling System (drug effects)
• Macrophages (cytology, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Phosphorylation
• Protein Tyrosine Phosphatases (genetics, metabolism)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• p38 Mitogen-Activated Protein Kinases (genetics, metabolism)