Complement Regulation Protein C1 Inhibitor Regulates Macrophage Polarization

Objective:To study regulation of complement regulation protein C1 inhibitor(C1INH)in macrophage polarization.Methods:After the isolated human monocytes were incubated with M-CSF or GM-CSF,these cells were induced with IFN-γ for M1 or IL-4+IL-13 for M2.CD14,CD162,and CD206 on the surface of M1 and M2 were detected by analysis of flow cytometry.The mRNA levels of chemokines and cytokines were analyzed by RT-PCR.CD 14 binding to Toll-like receptor 4(TLR4)in signaling events was examined by western blot.Results:C1INH regulated changes of CD14,CD163,and CD206 expression.C1INH decreased TNF-α and IL-6 in M1 and increased ALOX15 and IL-10 in M2.In addition,it inhibited expression of iNOS in Ml and level of Argl in M2.Improvement of bactericidal activity in M1 and phagocytosis function M2 was detected by C1INH administrated.C1INH blocked CD 14 binding to TLR4 in signaling events.C1INH enhanced levels of global DNA methylation and DNA methyltransferases(DNMTs)activity associated with one specific isoform of DNMT3b by activation of transcriptional factor Sp3,known to control DNMT3b activity.Furthermore,we demonstrated the regulation of C1INH in the distinct phenotypic differences of M1 and M2 by DNA methylation and DNMT3b activity associated with improvement of transcriptional factor,Sp3.Conclusion:C1INH may have a play in phenotype of polarized Ml and M2 by regulation of chemokine and cytokine secretion.Cl INH develops bactericidal activity and phagocytosis function.C1INH involves in inhibition of TLR4 signaling events.C1INH increases global DNA methylation and DNMTs activity.C1INH regulates DNMT3b activity by transcription factor Sp3.