2. Academic Validation
  3. Adipocyte-derived PAMM suppresses macrophage inflammation by inhibiting MAPK signalling

Adipocyte-derived PAMM suppresses macrophage inflammation by inhibiting MAPK signalling

  • Biochem J. 2015 Dec 15;472(3):309-18. doi: 10.1042/BJ20150019.
Fang Guo 1,  Hui He 1,  Zhi-Chao Fu 2,  Shengping Huang 3,  Tingtao Chen 2,  Christopher J Papasian 3,  Leslie R Morse 4,  Yan Xu 5,  Ricardo A Battaglino 5,  Xiao-Feng Yang 6,  Zhisheng Jiang 7,  Hong-Bo Xin 8,  Mingui Fu 9
Affiliations

Affiliations

  • 1 Department of Pathophysiology, The Institute of Cardiovascular Disease, University of South China, Hengyang, Hunan 421001, China Department of Basic Medical Science, School of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, U.S.A.
  • 2 Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi 330031, China.
  • 3 Department of Basic Medical Science, School of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, U.S.A.
  • 4 Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA 02115, U.S.A.
  • 5 Department of Mineralized Tissue Biology, The Forsyth Institute, Cambridge, MA 02142, U.S.A.
  • 6 Cardiovascular Research Center, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, U.S.A.
  • 7 Department of Pathophysiology, The Institute of Cardiovascular Disease, University of South China, Hengyang, Hunan 421001, China fum@umkc.edu hongbo.xin@yahoo.com zsjiang2005@163.com.
  • 8 Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi 330031, China fum@umkc.edu hongbo.xin@yahoo.com zsjiang2005@163.com.
  • 9 Department of Basic Medical Science, School of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, U.S.A. fum@umkc.edu hongbo.xin@yahoo.com zsjiang2005@163.com.
PMID: 26438880 DOI: 10.1042/BJ20150019
Abstract

Macrophages within adipose tissue play a key role in mediating inflammatory responses in adipose tissue that are associated with obesity-related metabolic complications. In an effort to identify novel proteins secreted from adipocytes that may negatively regulate macrophage inflammation, we found that peroxiredoxin (PRX)-like 2 activated in M-CSF stimulated monocytes (PAMM), a CXXC-type PRX-like 2 domain-containing redox regulatory protein, is a novel secreted protein with potent anti-inflammatory properties. PAMM is secreted from mature human adipocytes but not preadipocytes. Overexpression of PAMM significantly attenuated lipopolysaccharide (LPS)-induced macrophage inflammation. Incubation of macrophages with adipocyte-conditional medium treated with anti-PAMM antibody significantly enhanced LPS-induced interleukin-12 (IL-12) expression in Raw264.7 cells. In addition, incubation of Raw264.7 cells with purified PAMM protein had a similar anti-inflammatory effect. Moreover, forced expression of PAMM in Raw264.7 cells resulted in decreased LPS-induced ERK1/2, p38 and c-Jun N-terminal kinase (JNK) phosphorylation, suggesting that PAMM exerted the anti-inflammatory function probably by suppressing the mitogen-activated protein kinase (MAPK) signalling pathway. Mutations in the CXXC motif of PAMM that suppressed its anti-redox activity were still able to suppress production of inflammatory cytokines in LPS-stimulated macrophages, suggesting that PAMM's anti-inflammatory properties may be independent of its antioxidant properties. Finally, PAMM was highly expressed in both white (WAT) and brown adipose tissues (BAT) and further increased in obesity status. Our results suggest that adipocyte-derived PAMM may suppress macrophage activation by inhibiting MAPK signalling pathway.

Keywords

adipocyte; anti-inflammation; macrophage; peroxiredoxin-like 2 activated in M-CSF-stimulated monocytes (PAMM); redox; secreted protein.

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