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Kallikrein-binding protein inhibits LPS-induced TNF-α by upregulating SOCS3 expression

Authors

  • Zhiyu Dai,

    1. Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
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  • Lei Lu,

    1. Department of Biochemistry, Guangzhou Medical University, Guangzhou 510182, Guangdong Province, China
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  • Zhonghan Yang,

    1. Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
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  • Yuling Mao,

    1. Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
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  • Juling Lu,

    1. Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
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  • Cen Li,

    1. Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
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  • Weiwei Qi,

    1. Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
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  • Yifei Chen,

    1. Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
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  • Yachao Yao,

    1. Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
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  • Lei Li,

    1. Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
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  • Shaobo Chen,

    1. Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
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  • Yang Zhang,

    1. Department of Medical Laboratory, Guangdong General Hospital, Guangzhou 510080, Guangdong Province, China
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  • Weibin Cai,

    1. Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
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  • Xia Yang,

    Corresponding author
    1. Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
    2. China Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, Guangdong Province, China
    • Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou 510080, China.
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  • Guoquan Gao

    Corresponding author
    1. Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
    2. Key Laboratory of Functional Molecules from Marine Microorganisms (Sun Yat-sen University), Department of Education of Guangdong Province, Guangdong Province, China
    • Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou 510080, China.
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  • Zhiyu Dai and Lei Lu contributed equally to this study.

Abstract

Kallikrein-binding protein (KBP) was previously identified as a serpin family member with specific inhibitory effect on tissue kallikrein and angiogenesis, while there is little knowledge about the effects on inflammation. The aim of this study is to investigate whether KBP can suppress LPS-induced inflammatory process. Our results showed that both recombinant KBP and KBP overexpression inhibited LPS-stimulated TNF-α transcription and translation in macrophage cell line RAW264.7 and primary macrophages. Furthermore, KBP treatment protected mice from endotoxin shock and repressed serum TNF-α production, increasing survival rate of mice from 10% to 50% when compared to LPS alone. Moreover, qPCR and Western blot analysis demonstrated that both suppressor of cytokine signaling 3 (SOCS3) transcription and translation were induced by KBP treatment in the present of LPS. RNA interference assay and luciferase assay showed that SOCS3 was responsible for the down-regulation of TNF-α by KBP, rather than NF-κB subunit p65 and β-catenin. Therefore, we demonstrated that KBP suppressed LPS-induced TNF-α production via upregulating SOCS3 expression. These results present the protective effects of KBP on LPS-induced inflammation and provide novel information for the anti-inflammation mechanism. J. Cell. Biochem. 114: 1020–1028, 2013. © 2012 Wiley Periodicals, Inc.

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