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Resistin Up-Regulates COX-2 Expression via TAK1-IKK-NF-κB Signaling Pathway

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Abstract

The hormone resistin, which was originally shown to induce insulin resistance, has been implicated in the regulation of inflammatory processes, but the molecular mechanism underlying such regulation has not been clearly defined. The goal of our study was to determine whether the expression of COX-2 can be induced by resistin and what the potential signaling pathway involved in this process is. Compared with controls, resistin significantly upregulated COX-2 expression in RAW264.7 macrophage cells. Administration of anti-resistin antibody could significantly reduce this effect. Induction of COX-2 by resistin was also markedly reduced in the presence of either dominant negative mutant IκBα or PDTC, a pharmacological inhibitor of NF-κB. On the other hand, NF-κB subunit p65 was upregulated by resistin. Moreover, we found that transforming growth factor-β-activated kinase 1 (TAK1), a mitogen-activated protein kinase kinase kinase (MAPKKK), could be activated in response to resistin. These results suggest that resistin enhances COX-2 expression in mouse macrophage cells in a TAK1-IKK-NF-κB-dependent manner and therefore plays a critical role in inflammatory processes.

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Acknowledgements

This work was supported by the grants from Major Projects of National Science and Technology (2009ZX08009-151B), 973 (2006CB102100) Programme, 863 Programme (2008AA10Z134, 2006AA10Z140), High Education Doctorial Subject Research Programme (20060504016), General Programme (30771585, 30970356) and Key Programme of National Natural Science Foundation of China.

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Authors and Affiliations

  1. Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, HuaZhong Agricultural University, Wuhan, 430070, People’s Republic of China

    Jian Zhang, Ting Lei, Xiaodong Chen, Yin Peng, Huan Long, Lei Zhou, Jianfeng Huang, Zhilong Chen, Qinqiang Long & Zaiqing Yang

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  1. Jian Zhang
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Zhang, J., Lei, T., Chen, X. et al. Resistin Up-Regulates COX-2 Expression via TAK1-IKK-NF-κB Signaling Pathway. Inflammation 33, 25–33 (2010). https://doi.org/10.1007/s10753-009-9155-x

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