Macrophage polarization toward M1 phenotype through NE-κB signaling in patients with Behcet's disease

Background: Macrophages are key innate immune cells implicated in the pathogenesis of Behcet's disease (BD), and macrophage polarization plays a pivotal role in inflammatory response. This study aimed to investigate the role of BD serum on the phenotypes and functions of macrophage polarization. Methods: BD or HC serum-treated human monocyte-derived macrophages (HMDMs) were examined M1/M2 phenotypes using flow cytometry and ELISA. The phagocytic capacity of HMDMs and CD4(+)T cell differentiation facilitated by HMDMs were measured by flow cytometry. Transcriptome analysis of BD and HC serum-stimulated HMDMs was conducted to identify differentially expressed genes. NF-kappa B signaling was examined using western blot to explore the mechanism of macrophage polarization induced by BD serum. Results: BD serum-treated macrophages expressed a higher level of CD86, IL-12, and TNF-alpha and a lower level of CD163, which were compatible with the M1-like phenotype. Furthermore, BD serum-treated macrophages showed enhanced phagocytic capacity and promoted more Th1 cell differentiation. Sixty-one differentially expressed genes were identified between BD and HC serum-treated macrophages and were enriched in NF-kappa B signaling. BD serum-treated macrophages showed upregulated p-p65 and downregulated IKB alpha, and NF-kappa B inhibitor attenuated BD serum-stimulated M1-like phenotype. Conclusions: BD serum promoted macrophage polarization toward a proinflammatory M1-like phenotype through NF-kappa B signaling and potentially facilitated inflammation in BD. M1 polarized macrophages may be a potential therapeutic target for BD.

Automated summary

This study investigated the effect of BD serum on the phenotypes and functions of macrophage polarization. The findings revealed that BD serum promoted macrophage polarization towards a proinflammatory M1-like phenotype through NF-kappa B signaling. This may contribute to inflammation in BD. The study suggests that M1 polarized macrophages could be a potential therapeutic target for BD.