2. Academic Validation
  3. CD83 mediates the inhibitory effect of the S1PR1 agonist CYM5442 on LPS-induced M1 polarization of macrophages through the ERK-STAT-1 signaling pathway

CD83 mediates the inhibitory effect of the S1PR1 agonist CYM5442 on LPS-induced M1 polarization of macrophages through the ERK-STAT-1 signaling pathway

  • Int Immunopharmacol. 2024 Dec 25;143(Pt 3):113526. doi: 10.1016/j.intimp.2024.113526.
MeiHua Luo 1,  Wei Zhang 1,  Juan Yang 1,  Xi Du 2,  Xing Wang 3,  Guofeng Xu 3,  Hongmei Tang 3,  Zhibin Wang 3,  Xiaolin Zhong 4,  Jianguo Feng 5,  Ning Ma 6
Affiliations

Affiliations

  • 1 Inflammation & Allergic Diseases Research Unit, The Affiliated Hospital of Southwest Medical University, Luzhou 646000 Sichuan, China; Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000 Sichuan, China.
  • 2 Laboratory of Anesthesiology, Southwest Medical University, Luzhou 646000 Sichuan, China.
  • 3 Inflammation & Allergic Diseases Research Unit, The Affiliated Hospital of Southwest Medical University, Luzhou 646000 Sichuan, China.
  • 4 Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000 Sichuan, China.
  • 5 Laboratory of Anesthesiology, Southwest Medical University, Luzhou 646000 Sichuan, China. Electronic address: fengjianguo@swmu.edu.cn.
  • 6 Inflammation & Allergic Diseases Research Unit, The Affiliated Hospital of Southwest Medical University, Luzhou 646000 Sichuan, China. Electronic address: maning@swmu.edu.cn.
PMID: 39486189 DOI: 10.1016/j.intimp.2024.113526
Abstract

Macrophages possess M1/M2 polarization, which perform an essential role in immunology and inflammation studies. However, few studies have investigated the specific molecules involved in the polarization process beyond its induction and characterization. Here, we determined that the molecule S1PR1 regulates M1 polarization in macrophages and that the surface marker CD83 is involved in this process. The S1PR1 Agonist CYM5442 specifically increases CD83 expression in macrophages. Although the agonist CYM5442 and LPS regulate CD83 differently in macrophages, they have a synergistic effect that enhances CD83 expression. Notably, CYM5442 does not act synergistically with IL-4 regarding CD83 expression and does not affect IL-4-induced macrophage M2 polarization. Furthermore, CYM5442 inhibits the expression of LPS-induced inflammatory cytokines and the phosphorylation of ERK1/2 and STAT-1 in macrophages. However, this inhibition was significantly diminished or absent when CD83 is deficient, highlighting the importance of CD83 in mediating S1PR1 signaling in LPS-induced M1 polarization of macrophages. Overall, our findings provide valuable insights into the molecular mechanisms underlying macrophage polarization, particularly the roles of S1PR1 and CD83 in modulating inflammatory responses.

Keywords

CD83; Macrophages; Polarization; S1PR1 agonist.

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