Protective effects of pyrrolidine dithiocarbamate against airway inflammation in the ovalbumin-induced mouse model.
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.
Kwak
Hyun Jeong
HJ
Division of Cardiovascular disease, Department of Biomedical Sciences, National Institutes of Health, Nokbun-dong, Eunpyung-gu, Seoul 122-701, South Korea.
Song
Jin Sook
JS
Heo
Jun Yeong
JY
Yang
Sung Don
SD
Nam
Ji Yeon
JY
Cho
Young Sik
YS
Cheon
Hyae Gyeong
HG
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy; D004790:Enzyme Induction; D047209:Eosinophil Peroxidase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000037:antagonists & inhibitors; D015848:Interleukin-5 / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011524:Protoporphyrins / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology / Q000627:therapeutic use*; D013859:Thiocarbamates / Q000494:pharmacology / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D015848:Interleukin-5; D011524:Protoporphyrins; D011759:Pyrrolidines; D013859:Thiocarbamates; C017803:zinc protoporphyrin; D015847:Interleukin-4; C020972:pyrrolidine dithiocarbamic acid; D010047:Ovalbumin; D047209:Eosinophil Peroxidase; D051547:Heme Oxygenase-1