ELAVL1 increases macrophage M1 polarization via upregulating S100A8 to promote Crohn's disease progression.

OBJECTIVE

This study aims to investigate the impact and molecular mechanism of ELAVL1 in promoting macrophage M1 polarization in Crohn's disease (CD) by upregulating S100A8 expression.

METHODS

Peripheral blood mononuclear cells (PBMCs) from CD patients were collected to assess the expression of S100A8 and ELAVL1. The effect of ELAVL1/S100A8 on THP1 derived macrophage polarization and pro-inflammatory mediator secretion were evaluated via siRNA silencing and rescue experiments. RNA-binding protein immunoprecipitation (RIP) and RNA pull-down assays validated the interaction between ELAVL1 and S100A8.

RESULTS

Both S100A8 and ELAVL1 were significantly overexpressed in CD patients. Knockdown of S100A8 or ELAVL1 in M1-polarized macrophages marked reduced the expression of M1 biomarkers (CD80, CD86) and pro-inflammatory mediators. However, S100A8 overexpression reversed the inhibitory effects of ELAVL1 knockdown on M1 polarization, thereby promoting the M1 polarization and inflammatory response. RIP and RNA pull-down assays confirmed that ELAVL1 directly binds to S100A8 mRNA to regulate its expression.

CONCLUSION

ELAVL1 promotes M1 polarization of macrophages to exacerbate intestinal inflammation in CD via up-regulating S100A8 expression. These findings highlight the ELAVL1/S100A8 axis as a potential therapeutic target or diagnostic biomarker for managing CD.