Macrophage polarization toward M1 phenotype through NF-κB signaling in patients with Behçet's disease

• Published in: Arthritis research & therapy Vol. 24; no. 1
• Main Authors: Wu, Xiuhua, Wang, Zhimian, Shi, Jing, Yu, Xin, Li, Chaoran, Liu, Jinjing, Zhang, Fengchun, Chen, Hua, Zheng, Wenjie
• Format: Journal Article
• Language: English
• Published: BioMed Central Ltd 04.11.2022
• Subjects: Analysis; Behcet's disease; Care and treatment; Diagnosis; Health aspects; Macrophages; Phenotype; T cells; China
• ISSN: 1478-6354
• DOI: 10.1186/s13075-022-02938-z

Background Macrophages are key innate immune cells implicated in the pathogenesis of Behçet'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.sup.+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-κB 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-κB signaling. BD serum-treated macrophages showed upregulated p-p65 and downregulated IκB[alpha], and NF-κB inhibitor attenuated BD serum-stimulated M1-like phenotype. Conclusions BD serum promoted macrophage polarization toward a proinflammatory M1-like phenotype through NF-κB signaling and potentially facilitated inflammation in BD. M1 polarized macrophages may be a potential therapeutic target for BD. Keywords: Behçet's disease, Macrophage polarization, Phagocytosis, Th1 differentiation, NF-κB pathway