Macrophage polarization is closely related to inflammation development, yet how macrophages are polarized remains unclear. In our study, the number of M1 macrophages was markedly increased in Fam76b knockout U937 cells vs. wild-type U937 cells, and FAM76B expression was decreased in M1 macrophages induced from different sources of macrophages. Moreover, Fam76b knockout enhanced the mRNA and protein levels of M1 macrophage-associated marker genes. These results suggest that FAM76B inhibits M1 macrophage polarization. We then further explored the mechanism by which FAM76B regulates macrophage polarization. We found that FAM76B can regulate PI3K/Akt/NF-κB pathway-mediated M1 macrophage polarization by stabilizing PIK3CD mRNA. Finally, FAM76B was proven to protect against inflammatory bowel disease (IBD) by inhibiting M1 macrophage polarization through the PI3K/Akt/NF-κB pathway in vivo. In summary, FAM76B regulates M1 macrophage polarization through the PI3K/Akt/NF-κB pathway in vitro and in vivo, which may inform the development of future therapeutic strategies for IBD and other inflammatory diseases.

巨噬细胞极化与炎症发展密切相关，但巨噬细胞如何极化仍不清楚。在我们的研究中，与野生型U937细胞相比， Fam76b敲除的U937细胞中M1巨噬细胞的数量显着增加，并且在不同来源的巨噬细胞诱导的M1巨噬细胞中FAM76B表达降低。此外， Fam76b敲除增强了 M1 巨噬细胞相关标记基因的 mRNA 和蛋白质水平。这些结果表明 FAM76B 抑制 M1 巨噬细胞极化。然后我们进一步探讨了FAM76B调节巨噬细胞极化的机制。我们发现 FAM76B 可以通过稳定 PIK3CD mRNA 来调节 PI3K/Akt/NF-κB 通路介导的 M1 巨噬细胞极化。最后，FAM76B 被证明可以通过体内 PI3K/Akt/NF-κB 通路抑制 M1 巨噬细胞极化，从而预防炎症性肠病 (IBD)。总之，FAM76B 在体外和体内通过 PI3K/Akt/NF-κB 通路调节 M1 巨噬细胞极化，这可能为 IBD 和其他炎症性疾病未来治疗策略的开发提供信息。