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Selective Involvement of Reactive Oxygen Intermediates in Platelet-activating Factor-mediated Activation of NF-κB

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Abstract

Although it has been suggested that some biological activities of platelet-activating factor (PAF) are mediated by, at least in part, reactive oxygen intermediates (ROI), the precise mechanisms underlying the interaction between the two remains to be elucidated. Antioxidants, such as α-tocopherol acid succinate, N-acetyl-L-Cysteine, pyrrolidinedithiocarbamate failed to inhibit PAF-induced immediate systemic reactions such as lethality, symptoms of disseminated intravascular coagulation, and histological changes such as pulmonary edema and hemorrhage in renal medullae 10 min following PAF injection. In contrast, antioxidants significantly inhibited both the in vivo and in vitro PAF-induced NF-κB activation and NF-κB-dependent TNF-α expression. The effects of the antioxidants were due to their inhibition of PAF-induced degradation of IκBα, a protein responsible for keeping NF-κB in an inactive form. A protein tyrosine kinase and N-tosyl-L-phenylalanine chloromethyl ketone sensitive serine protease were involved in both PAFand H2O2-induced NF-κB activation. Collectively, these data indicate that the PAF-induced NF-κB activation is selectively mediated through the generation of ROI.

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Authors and Affiliations

  1. Department of Biological Science,College of Natural Sciences, Chonnam National University, Kwangju, Republic of Korea

    Jung Hwa Choi, Woon Jae Chung, Su Ji Han, Hwanghee Blaise Lee & Suhn Young Im

  2. Department of Immunology, Institute for Medical Sciences, Chonbuk National University Medical School, Chonju, Korea

    Il Whan Choi & Hern Ku Lee

  3. Department of Pathology, Institute for Medical Sciences, Chonbuk National University Medical School, Chonju, Korea

    Kyu Yun Jang & Dong Geun Lee

  4. Korean Research Institute of Chemical Technology, Daejon, Korea

    Sang Seop Han

  5. Department of Biology Education, Chonbuk National University, Chonju, Korea

    Kyung Hwa Park

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Choi, J.H., Chung, W.J., Han, S.J. et al. Selective Involvement of Reactive Oxygen Intermediates in Platelet-activating Factor-mediated Activation of NF-κB. Inflammation 24, 385–398 (2000). https://doi.org/10.1023/A:1007068010645

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