Heme Oxygenase-1 Alleviates Allergic Airway Inflammation By Regulating CD4~+T Subsets

?Objectices? To explore the role of heme oxygenase-1(HO-1) alleviating allergic airway inflammation and regulating T helper cells(Th) 1, Th2, Th17 and regulatory T cells(Tregs) in a mouse model of asthma. ?Methods?Balb/C mice were sensitized and challenged with ovalbumin(OVA) to induce airway inflammation. Hemin, the substrate of HO-1, was administered to up-regulate HO-1 expression. 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-1 protein expression in lung and 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 lung were measured by real-time PCR. ?Results?The results showed that the expression of HO-1 in lung and spleen was increased in OVA group compared with the control group, which was further increased by hemin treatment(OVA+Hemin group). The pulmonary histopathology revealed that there were obvious inflammatory cell infiltrates, mainly consisting of eosinophils(EOS) in OVA group. However,this phenomenon could be markedly alleviated by hemin. In lung tissues, the mRNA expressions of T-bet and IFN-? were down-regulated, while the mRNA expressions of GATA-3, ROR?t, IL-4, IL-17 A and IL-6 in OVA group were much higher than those in the control group. However, administration of hemin could reverse the results above. Furthermore, the mRNA expressions of Foxp3, IL-10 and TGF-? were significantly higher in OVA+Hemin group compared with the other two groups. A mass of Th2 cells were observed in OVA group accompanied by a slight increased Th17 cells and a decrease in Th1 and Treg cells in spleen. Hemin treatment could significantly reverse the results above. Our data demonstrated that induction of HO-1 might alleviate eosinophilic airway inflammation by regulating the balance of Th1/Th2 and Th17/Treg cells as well as promote TGF-? and IL-10 productions to suppress airway inflammation in asthma.