Sulfur dioxide exposure enhances Th2 inflammatory responses via activating STAT6 pathway in asthmatic mice

Sulfur dioxide (SO2) is one of potential risk factors for induction and/or exacerbation of asthma, but the underlying mechanisms are not well understood. In this study, we investigate the role of SO2 in asthma using a classical asthmatic model with allergic airway inflammation by treating C57BL/6 mice with ovalbumin (OVA) and/or 10 mg/m(3) SO2. Our results showed that SO2 exposure alone induced slight pathological changes but did not significantly increase inflammatory cell counts, pro-inflammatory cytokine expression, and mucus production in the airway of mice, whereas SO2 exposure in OVA-induced asthmatic mice caused marked pulmonary pathological changes and significantly increased the counts of eosinophil-rich leukocytes compared with OVA alone asthmatic mice. The expression of MUC5AC, TNF-alpha, Th2 cytokines (IL-4, IL-5, and IL-13) and STAT6 was further up-regulated in OVA plus SO2 treated mice compared with OVA alone treated mice. In addition, exposure to SO2 alone markedly elevated STAT6 mRNA levels and hydrogen peroxide (H2O2) content in the lung. These findings suggest that SO2 amplifies Th2 inflammatory responses in OVA-induced asthmatic mice by activating STAT6, which can further induce Th2 cytokine expression. Induction of STAT6 expression might be an important mechanism underlying the increased risk for asthma after environmental exposure.