Selective inhibition of inflammatory cytokine storm in macrophages by α-momorcharin
- Author:
Cheng LI
1
;
Fu-Bing SHEN
1
;
Jia-Cong CHENG
2
;
Chen-Xin YE
2
;
Yao LIU
2
;
Ke-Jun PENG
2
;
Fu-Bing SHEN
2
;
Su-Hang TAN
3
Author Information
- Publication Type:Journal Article
- Keywords: cytokine storm; inflammatory macrophages; LRP1 receptor; macrophage activation syndrome; TLR4 signaling pathway; α-momorcharin
- From: Chinese Pharmacological Bulletin 2023;39(10):1846-1852
- CountryChina
- Language:Chinese
- Abstract: Aim To observe the inhibitory effect of Alpha-momorcharin (α-MMC) on the inflammatory cytokine storm of Ml-type inflammatory macrophages induced by LPS and explore its possible targeting mechanism. Methods Western blot was used to detect the expression of WIL2-S B lymphocytes, H9 T lymphocytes, THP-1 monocytes and M0 macrophages LRP1 receptor protein. CCK-8 method was used to detect the survival rate of the four cells. ELISA was used to detect the expression level of inflammatory cytokines in Ml macrophages. Western blot was used to detect the expression of TLR4 signaling pathway-related protein in Ml macrophages. Results Macrophages had a high density of LRP1 receptors consistent with monocytes; the survival rate of α-MMC on the four cells was positively correlated with the density of this receptor; α-MMC inhibited the expression of inflammatory cytokinesTNF-α, IL-lβ, IL-6, IL-8, MlP-lα and MCP-1 in Ml macrophages in a dose-and time-dependent manner; α-MMC showed significant inhibition to TAKl/pTAK1, p-JNK, p-APl and p-p65 signaling proteins of the TLR4 signaling pathway, and this inhibition could be blocked by the LRP1 receptor blocker RAP. Conclusions α-MMC selectively inhibits macrophage inflammatory cytokine synthesis by inhibiting TAK1 of the TLR4 signaling pathway, which in turn inhibits the downstream NF-ΚB and MAPK pathways, mediated by the LRP1 receptor. The selective immunosuppressive effect of α-MMC on macrophages may make it a very promising agent for the treatment of acute infectious macrophage activation syndrome (MAS).
