DEP(Diesel Exhaust Particles) Or CSE(Cigarette Smoke Extract) Inhibits The Regulation Function Of Interleukin 27 On Asthma Macrophage By Down Regulating The Expression Of WSX-1 On Asthma Macrophage

Background: Asthma is a chronic airway inflammation disease.A variety of cells such as lymphocytes,macrophage,epithelial cells have participated in this processes,in which macrophage have a vital role in the mechanism of asthma.The maturation and polarization of macrophage need some different kinds of cytokines,granulocyte-macrophage colony stimulating factor(GM-CSF)is a potent stimulator for the polarization of macrophage into the M1 phenotype.IL-27 is a member of the family of IL-12,its receptor(IL-27R)consisting of WSX-1 and GP130,which is mainly expressed on the surface of macrophage and some other immune cells.IL-27 can enhance the phagocytosis function and inflammatory secretion of macrophage by combining with its receptors on macrophage.It can also regulate the balance of Th1 and Th2 responses,so IL-27 might be important in the pathogenesis of asthma as well.Diesel exhaust particulate(DEP)and Cigarette smoke extract(CSE)are the most common atmospheric pollutants.Studies showed that the exacerbation of symptoms and increased risk of acute attacks in asthma patients is significantly associated with the exposure of DEP or CSE.These kinds of exposures may also lead to glucocorticoid(GC)resistance in asthma patients as well.However,studies about the effect of DEP or CSE on the function of IL-27 have not been reported.This study aims at exploring whether the regulation of IL-27 on the function of asthma macrophage will be affected when exposing to DEP or CSE.We also explore whether GM-CSF and GC can reverse these influences under DEP or CSE exposure.Methods: Mouse macrophage cell lines(RAW264.7)were cultured in vitro and recombinant mouse IL-4 was used to simulate the inflammatory environment of asthma.DEP or CSE exposure was performed combined with IL-4 or not.Expression of WSX-1 on RAW264.7 in the combined treatment group and other groups was detected by q PCR or Flow cytometry to determine the effect of DEP or CSE treatment on expression of WSX-1 on the surface of asthma macrophage.Exogenous IL-27 was performed after the treatment to detect the m RNA expression of IP-10.And the phagocytosis ability of RAW264.7 was reflected by the phagocytosis rate of RAW264.7 on chicken erythrocytes and BCG vaccine.At the same time.Intervention methods were taken in vitro,intervention was conducted with GM-CSF and GC,the expression of WSX-1 and the ability of IL-27 to regulate macrophage function were detected in the combined treatment group.Results: 1.When treated with DEP or CSE combined with IL-4,the expression of WSX-1 on the surface of macrophage in the combined treatment group was significantly inhibited compared with that in the normal control group,the treated group alone,and the asthma non-treated group.2.After adding exogenous IL-27 stimulation,the expression of IP-10 is restrained in DEP or CSE combined treatment group,the phagocytosis rate of chicken red blood cells and the BCG vaccine were all decreased in the combined treatment group when compared with other groups;3.After GM-CSF intervention,the inhibited effect of WSX-1 expression in the combined treatment group was reversed,and the regulating effect of IL-27 on macrophage function returned to normal.Low concentration of GC intervention treatment can partly recover the regulation of IL-27 on macrophage function but not influence WSX-1 expression in the combined group while high concentration of GC intervention therapy can not recover the regulating effect of IL-27 on asthma macrophage function nor change the expression of WSX-1 on asthma macrophage in the combined group.Conclusion: DEP or CSE can inhibit the promoting effect of IL-27 on the secretion of IP-10 and phagocytosis ability of asthma macrophage by down-regulating the expressing of WSX-1 on macrophage.Exogenous GM-CSF treatment can promote the expression of WSX-1 on the surface of asthma macrophage and restore the regulatory effect of IL-27 on macrophage in the combined treatment group.GC treatment can partially restore the regulatory effect of IL-27 on macrophage function at low concentrations,but cannot restore the regulatory effect at high concentrations.