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Research ArticleArticle

Antioxidant Down-Regulates Interleukin-18 Expression in Asthma

Kyung Sun Lee, So Ri Kim, Seoung Ju Park, Kyung Hoon Min, Ka Young Lee, Sun Mi Jin, Wan Hee Yoo and Yong Chul Lee
Molecular Pharmacology October 2006, 70 (4) 1184-1193; DOI: https://doi.org/10.1124/mol.106.024737
Kyung Sun Lee
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So Ri Kim
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Seoung Ju Park
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Kyung Hoon Min
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Ka Young Lee
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Sun Mi Jin
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Wan Hee Yoo
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Yong Chul Lee
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Abstract

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 α-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-κB (NF-κB), activity. These results indicate that antioxidants may reduce IL-18 expression in asthma by inhibiting the activity of NF-κB and suggest that ROS regulate the IL-18 expression.

Footnotes

  • This work was supported by a grant from the National Research Laboratory Program of the Korea Science and Engineering Foundation, by Korea Research Foundation Grant funded by Korea Government (MOEHRD, Basic Research Promotion Fund) (KRF-2005-201-E00014), by a grant of the Korea Health 21 R&D project, Ministry of Health and Welfare, Republic of Korea (A060169) (to Y.C.L.), and by a grant from the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (0412-CR03-0704-0001) (to S.J.P.).

  • K.S.L. and S.R.K. contributed equally to this work.

  • ABBREVIATIONS: ROS, reactive oxygen species; Th, T-helper cell; OTC, l-2-oxothiazolidine-4-carboxylic acid; BAL, bronchoalveolar lavage; RL, Airway resistance; NF-κB, nuclear factor-κB; IL, interleukin; GSSG, glutathione disulfide; GSH, glutathione; RT-PCR, reverse transcription-polymerase chain reaction; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; OVA, ovalbumin; BAY 11-7085, (E)-3[(4-t-butylphenyl)sulfonyl]-2-propenenitrile; buffer A, Tris-HCl, EDTA, glycerol, dithiothreitol, MgCl2, and phenylmethylsulfonyl fluoride; buffer B, sucrose, MgCl2, and potassium phosphate buffer.

    • Received March 21, 2006.
    • Accepted July 5, 2006.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 70 (4)
Molecular Pharmacology
Vol. 70, Issue 4
1 Oct 2006
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Research ArticleArticle

Antioxidant Down-Regulates Interleukin-18 Expression in Asthma

Kyung Sun Lee, So Ri Kim, Seoung Ju Park, Kyung Hoon Min, Ka Young Lee, Sun Mi Jin, Wan Hee Yoo and Yong Chul Lee
Molecular Pharmacology October 1, 2006, 70 (4) 1184-1193; DOI: https://doi.org/10.1124/mol.106.024737

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Research ArticleArticle

Antioxidant Down-Regulates Interleukin-18 Expression in Asthma

Kyung Sun Lee, So Ri Kim, Seoung Ju Park, Kyung Hoon Min, Ka Young Lee, Sun Mi Jin, Wan Hee Yoo and Yong Chul Lee
Molecular Pharmacology October 1, 2006, 70 (4) 1184-1193; DOI: https://doi.org/10.1124/mol.106.024737
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