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IFN-γ synergizes with LPS to induce nitric oxide biosynthesis through glycogen synthase kinase-3-inhibited IL-10 by Chiou-Feng Lin; Cheng-Chieh Tsai; Wei-Ching Huang; Chi-Yun Wang; Hsiang-Chi Tseng; Yi Wang; Jui-In Kai; Szu-Wen Wang; Yi-Lin Cheng is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
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## Abstract Interferon‐γ (IFN‐γ) plays a crucial role in innate immunity and inflammation. It causes the synergistic effect on endotoxin lipopolysaccharide (LPS)‐stimulated inducible nitric oxide synthase (iNOS)/NO biosynthesis; however, the mechanism remains unclear. In the present study, we investigated the effects of glycogen synthase kinase‐3 (GSK‐3)‐mediated inhibition of anti‐inflammatory interleukin‐10 (IL‐10). We found, in LPS‐stimulated macrophages, that IFN‐γ increased iNOS expression and NO production in a time‐dependent manner. In addition, ELISA analysis showed the upregulation of tumor necrosis factor‐α and regulated on activation, normal T expressed and secreted, and the downregulation of IL‐10. RT‐PCR further showed changes in the IL‐10 mRNA level as well. Treating cells with recombinant IL‐10 showed a decrease in IFN‐γ/LPS‐induced iNOS/NO biosynthesis, whereas anti‐IL‐10 neutralizing antibodies enhanced this effect, suggesting that IL‐10 acts in an anti‐inflammatory role. GSK‐3‐inhibitor treatment blocked IFN‐γ/LPS‐induced iNOS/NO biosynthesis but upregulated IL‐10 production. Inhibiting GSK‐3 using short‐interference RNA showed similar results. Additionally, treat
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- Author
- Chiou-Feng Lin; Cheng-Chieh Tsai; Wei-Ching Huang; Chi-Yun Wang; Hsiang-Chi Tseng; Yi Wang; Jui-In Kai; Szu-Wen Wang; Yi-Lin Cheng
- Publisher
- John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0730-2312)
- Published
- 2008
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)