Abstract
Pyrrolidine dithiocarbamate (PDTC) is known to exert anti-tumor and anti-inflammatory effects. However, the effects of PDTC against airway inflammation and its underlying mechanisms have not been reported. In the present study, we examined the protective effects of PDTC in a murine model of asthma induced by ovalbumin. PDTC reduced the number of infiltrating inflammatory cells in concert with reduced eosinophil peroxidase (EPO) activity in bronchoalveolar lavage fluid. In parallel, PDTC decreased airway hyperresponsiveness in a dose dependent manner. All these effects were correlated with heme oxygenase-1 (HO-1) mRNA and protein induction, and reversed by ZnPP, a HO-1 inhibitor. In addition, PDTC reduced the secretion of Th 2 cytokines such as IL-4 and IL-5, whereas ZnPP blocked the inhibitory effects of PDTC on Th 2 cytokine secretion. These results suggest that PDTC protects against airway inflammation at least in part via HO-1 induction, and that inhibitory action on Th 2 cytokines may be associated with the protective mechanism of PDTC.
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