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CD200 increases alternatively activated macrophages through cAMP‐response element binding protein – C/EBP‐beta signaling
Author(s) -
Hayakawa Kazuhide,
Wang Xiaohua,
Lo Eng H.
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13492
Subject(s) - creb , cyclic amp response element binding protein , signal transduction , ccaat enhancer binding proteins , microbiology and biotechnology , macrophage polarization , lipopolysaccharide , biology , macrophage , transcription factor , immunology , biochemistry , nuclear protein , in vitro , gene
The concept of macrophage polarization toward different phenotypes after CNS injury has been increasingly discussed. Here, we propose that CD200 treatment may help shift pro‐inflammatory macrophages to an arginase 1 (Arg1)‐, transglutaminase 2 ( TGM 2)‐, and transforming growth factor beta 1 ( TGF ‐β)‐positive phenotype. Rat macrophages were stimulated by interferon γ and lipopolysaccharide ( LPS ) to induce pro‐inflammatory phenotypes. Treatment with human CD200‐Fc up‐regulated expression levels of alternatively activated M2‐like markers such as Arg1 and TGM2 but suppressed pro‐inflammatory M1‐like markers such as toll‐like receptor 4, interleukin 1 beta (IL‐1β), IL‐6, and GM ‐ CSF . Concomitantly, CD200‐Fc enhanced (CCAAT/enhancer‐binding protein) C/ EBP ‐beta promoter activity, whereas NF‐κB activity was suppressed. Treatment with CD200‐Fc also up‐regulated potentially beneficial TGF ‐β expression in macrophages. When C/ EBP ‐beta signaling was suppressed with siRNA, the effect of CD200‐Fc on Arg1, TGM 2 and TGF ‐β up‐regulation was canceled. Taken together, these data provide proof‐of‐principle that targeting CD200 signaling may be a novel therapeutic approach to shift macrophages toward M2‐like polarization via modulating c AMP ‐response element binding protein‐C/ EBP ‐beta transcriptional activity.We showed that CD200 treatment decreased pro‐inflammatory cytokines (IL‐1β, IL‐6, and GM‐CSF) along with suppressed inflammatory NF‐κB activity in pro‐inflammatory Mφ. On the other hand, CD200 increased Arg1, TGM2, and TGF‐β production through CREB‐C/EBPβ signaling. We think that these findings provide proof‐of‐concept that CD200 signaling may play a key role in regulating macrophage polarization toward anti‐inflammatory phenotypes.