The role of C/EBP homologous protein (CHOP) in regulating macrophage polarization in RAW264.7 cells

Schistosomiasis is a zoonotic parasitic disease that is endemic in Asia. Macrophages are mainly involved in the inflammatory response of late schistosoma infection. Our previous study found that C/EBP homologous protein (CHOP) expression is significantly increased, and M2 macrophages are activated in schistosome-induced liver fibrosis mice. However, the role of CHOP in the regulation of macrophage polarization remains to be further studied. Western blotting or quantitative PCR revealed that IL-4 increased the expression of arginase-1, macrophage mannose receptor 1, phosphorylation signal transducer and activator of transcription 6 (p-STAT6), Kruppel-like factor 4 (KLF4), CHOP, and IL-13 receptor alpha (IL-13R alpha) and induced M2 polarization in RAW264.7 as measured by flow cytometry. Inhibiting STAT6 phosphorylation (AS1517499) reduced the IL-4-induced expression of KLF4, CHOP, and IL-13R alpha and also the number of M2 macrophages. The overexpression of CHOP stimulated M2 polarization, but AS1517499 inhibited this effect. CHOP increased the protein expression of KLF4 but did not change the expression of p-STAT6. Soluble egg antigen (SEA) could promote the IL-4-induced protein expression of p-STAT6, CHOP, and KLF4. Overall, the findings show that SEA can promote the activation of M2 macrophages by causing increased CHOP-induced KLF4 levels and activation of STAT6 phosphorylation.