Heme oxygenase-1 (HO-1) has anti-inflammatory effects in asthma. CD4+CD25high regulatory T cells (Treg) are a potent immunoregulator that suppresses the immune response. We studied the effects of HO-1-mediated CD4+CD25high Treg on suppression of allergic airway inflammation by comparing mice treated with hemin, OVA, Sn-protoporphyrin (SnPP), and hemin plus SnPP. Airway responsiveness, airway eosinophil infiltration, the level of OVA-specific IgE, and the numbers of cells in general and eosinophils in particular in bronchial alveolar lavage fluid were lower in the hemin group than in the OVA, SnPP, and hemin plus SnPP groups. The expressions of HO-1 mRNA and protein in the lung were increased by repeated administrations of hemin and SnPP. However, the activity of HO-1 was highest in hemin mice. The percentage and suppressive function of CD4+CD25high Treg and the expression of Foxp3 mRNA were obviously enhanced after treatment with hemin. This increase was diminished by the administration of SnPP. The concentration of serum IL-10 was higher in the hemin group than in the other groups, whereas the level of serum TGF-β did not significantly differ across groups. Furthermore, the ratio of IFN-γ/IL-4 mRNA in the lung was higher in hemin-treated mice than in OVA and SnPP mice. The suppressive capacity of CD4+CD25high Treg was not enhanced in the IL-10-deficient mice treated with hemin. In conclusion, our experiments in the animal model demonstrated that HO-1 has anti-inflammatory effects, probably via enhancement of the secretion of IL-10 and promotion of the percentage of CD4+CD25high Treg.

Asthma is an airway disease characterized by recurrent inflammation. It occurs in all age groups and is ranked as one of the most prevalent noninfectious diseases. It is estimated that 160 million people worldwide suffer with asthma. Despite 20 years of effort, the morbidity and mortality rates of asthma have been rising all throughout the world. As a result, our society bears significant health and economic burdens for the disease. Therefore, it is imperative to understand fully the pathogenesis of asthma and develop novel preventive/therapeutic strategy. Heme oxygenase (HO) is a rate-limiting enzyme for heme metabolism. It catalyzes heme into equivalent amounts of biliverdin, carbon monoxide (CO), and free iron. At present, there are three known isoenzymes of HO: inducible HO-1, constitutive HO-2, and a newly found isomer HO-3.

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