Antioxidant down-regulates interleukin-18 expression in asthma.
An alteration in the balance between a T-helper type 2 cell (Th2) response and a Th1 response may predispose to the development of bronchial asthma. Interleukin-18 (IL-18) has an ability to promote both Th1 and Th2 responses, depending on the surrounding cytokine environment. Reactive oxygen species (ROS) play a crucial role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of asthma. In this study, we used a C57BL/6 mouse model of allergic asthma to examine the effects of antioxidants on the regulation of IL-18 expression. Our present study with ovalbumin-induced murine model of asthma revealed that ROS production in cells from bronchoalveolar lavage fluids was increased and that administration of L-2-oxothiazolidine-4-carboxylic acid or alpha-lipoic acid reduced the increased levels of ROS, the increased expression of IL-18 protein and mRNA, airway inflammation, and bronchial hyperresponsiveness. Our results also showed that antioxidants down-regulated a transcription factor, nuclear factor-kappaB (NF-kappaB), activity. These results indicate that antioxidants may reduce IL-18 expression in asthma by inhibiting the activity of NF-kappaB and suggest that ROS regulate the IL-18 expression.
Lee
Kyung Sun
KS
Department of Internal Medicine, Chonbuk National University Medical School, San 2-20, Geumamdong, Deokjin-gu, Jeonju, Jeonbuk 561-180, South Korea.
Kim
So Ri
SR
Park
Seoung Ju
SJ
Min
Kyung Hoon
KH
Lee
Ka Young
KY
Jin
Sun Mi
SM
Yoo
Wan Hee
WH
Lee
Yong Chul
YC
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001249:Asthma / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015536:Down-Regulation; D005260:Female; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin; D012333:RNA, Messenger / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism
D000975:Antioxidants; D020382:Interleukin-18; D007378:Interleukins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; D007073:Immunoglobulin E; D008063:Thioctic Acid; D010047:Ovalbumin; D005978:Glutathione; D019803:Glutathione Disulfide