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The melanocortin 1 receptor (MC1R) inhibits the inflammatory response in Raw 264.7 cells and atopic dermatitis (AD) mouse model

Molecular Biology Reports volume 40, pages 1987–1996 (2013)Cite this article

Abstract

The alpha melanocyte stimulating hormone receptor (MC1R) is one of five G-protein coupled receptors belonging to the melanocortin subfamily, MC1R gene has been known to play a major role in regulating of fur color in mammals, and α-MSH and ACTH are endogenous nonselective agonists for MC1R. However, we found that MC1R was highly expressed in Raw 264.7 cells which were important inflammatory cells involved in the initiation of inflammatory responses. In addition, Cyclic AMP is not only a key molecule in the MC1R signal transduction pathway, but dampen innate immune-mediated responses. These intriguing biological results triggered the further conformation studies; it suggested that MC1R was very likely to be an important role in immunoregulation. In this study, we were to investigate the immunosuppressive effects of MC1R on inflammation in lipopolysaccharide (LPS) stimulated Raw 264.7 cells and LPS induced vivo 2-chloro-1,3,5-trinitrobenzene (TNCB)-induced atopic dermatitis (AD) model. The effects of the MC1R antagonist psoralen on pro-inflammatory cytokines and signaling pathways were analyzed by enzyme-linked immunosorbent assay, western blot, real-time fluorescence quantitative PCR and Histological analysis. Our results show a consistent and marked effect of high concentrations of MC1R antagonist psoralen increased the level of MC1R mRNA in Raw 264.7 cells by cumulative feedback regulation through preferential binding of MC1R. Moreover, as evidenced by inhibiting the LPS-induced TNF-α, IL-6 and enhancing the expression level of cyclic AMP protein in vitro. In vivo study it was also observed that psoralen promoted on histopathologic changes in the skin tissue of TNCB-induced AD mice. Taken together, our results suggest that MC1R decrease the inflammation in vitro and vivo, and might be a therapeutic signaling pathway to against inflammatory diseases.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (NSFC) (Nos. 30800807 and 31072097) and the Special Foundation for Postdoctor of China Ministry of Education (No. 20100471261).

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Affiliations

  1. College of Animal Science and Veterinary Medicine, Jilin University, 130062, Changchun, China

    Wei Chen, Hai’e Qu, Zhou Song, Zhanqing Yang, Qinghua Huang, Meixia Huo, Bo Liu & Qiaoling Zhang

  2. College of Animal Science and Technology, Jilin Agricultural University, 130118, Changchun, China

    Jianping Li & Huaizhi Jiang

  3. Faculty of Animal Science and Technology, Yunnan Agricultural University, 650201, Kunming, China

    Jinlong Huo

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  1. Wei Chen
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  2. Jianping Li
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Correspondence to Qiaoling Zhang.

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Wei Chen and Jianping Li contributed equally to this study.

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Chen, W., Li, J., Qu, H. et al. The melanocortin 1 receptor (MC1R) inhibits the inflammatory response in Raw 264.7 cells and atopic dermatitis (AD) mouse model. Mol Biol Rep 40, 1987–1996 (2013). https://doi.org/10.1007/s11033-012-2256-x

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  • DOI: https://doi.org/10.1007/s11033-012-2256-x

Keywords

  • MC1R
  • Cytokines
  • Inflammation action
  • Psoralen
  • Atopic dermatitis