Heme oxygenase-1 alleviates allergic airway inflammation by regulating CD4~+T subsets
YUAN Yu-fan;LIU Qi;ZHANG Yan-jie;DI Cai-xia;LIN Xiao-liang;ZHOU Tong;XIA Zhen-wei;Department of Pediatrics,Ruijin Hospital Affiliated to Jiaotong University School of Medicine;
To explore the role of heme oxygenase-1(HO-1)in alleviating allergic airway inflammation and regulating Th cells(T helper cells,Th)1,Th2,Th17 and regulatory T cells(Tregs)in a mouse model of asthma,BALB/c mice were sensitized and challenged with ovalbumin(OVA)to induce eosinophilic airway inflammation.Hemin,the substrate of HO-1,was administered to up-regulate HO-1expression.The analysis of pulmonary histopathology,serum OVA-specific IgE level and the inflammatory cell differential in bronchial alveolar lavage fluid(BALF)were detected to evaluate the airway inflammation.HO-1protein expression in the lung and the spleen was detected by Western blot and real-time PCR.CD4+T cell subsets were analyzed by flow cytometry.The mRNA levels of cytokines and specific transcription factors associated with Th1,Th2,Th17 and Treg cells in the lung were measured by real-time PCR.The results showed that the expression of HO-1in the lung and spleen was increased in OVA group compared with the control group,which was further elevated by hemin treatment(OVA+Hemin group).The pulmonary histopathology revealed that there were obvious inflammatory cell infiltrates,consisting mainly of eosinophils(EOS)in OVA group.Meanwhile,the total number of cells in BALF and the level of serum OVA-specific IgE were elevated.These OVA-induced changes were markedly reduced by hemin treatment.In lung tissues,the mRNA expressions of T-bet and IFN-γwere down-regulated,while the mRNA expressions of GATA-3,RORγt,IL-4,IL-17 Aand IL-6were much higher in OVA group than those in the control group.Also,administration of hemin could reverse the above results.Furthermore,the mRNA expressions of Foxp3,IL-10 and TGF-βwere significantly higher in hemin+OVA group compared with the other two groups.CD4+T cell subsets in the spleen showed that a mass of Th2 cells were observed in OVA group accompanied by a slight increase in Th17 cells and a decrease in Th1 and Treg cells.Hemin treatment significantly reduced the percentages of Th2 and Th17cells and promoted percentage of Treg cells.The percentage of Th1 cells presented an increasing trend in hemin+OVA group.Our data demonstrate that induction of HO-1might alleviate eosinophilic airway inflammation by regulating the balance of Th17/Treg and Th1/Th2 cells as well as promote TGF-βand IL-10 production to suppress airway inflammation in asthma.
【Fund】： 国家自然科学基金(81270084;81070022);; 上海市科委项目(13XD1402800)
【CateGory Index】： R562.25
【CateGory Index】： R562.25