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N-terminal domain of EcC1INH in Epinephelus coioides can antagonize the LPS-stimulated inflammatory response

Luo, Sheng-Wei, Kang, Huan, Xie, Ren-Chong, Wei, Wei, Liang, Qing-jian, Liu, Yuan, Wang, Wei-Na
Fish & shellfish immunology 2019 v.84 pp. 8-19
Epinephelus coioides, Vibrio alginolyticus, complement, complementary DNA, cytokines, fish, gene expression, inflammation, kidneys, liver, messenger RNA, polymerase chain reaction, proteinases, shellfish, signal transduction
Complement 1 inhibitor (C1INH) serving as a multifunctional factor can participate in the regulation of complement cascades and attenuate the activation of various proteases. In this study, we obtained EcC1INH cDNA and the tissue-specific analysis indicate that the highest expression level of EcC1INH mRNA was detected in liver. Moreover, Vibrio alginolyticus challenge can significantly increase EcC1INH mRNA expression in liver and kidney. N-terminal domain of EcC1INH could decrease LPS binding activity to cell surface, while loss of positively charged residues (PCRs) Arg21, His22, Lys50, Arg61 in N-terminal domain of EcC1INH can significantly reduce its interaction with LPS. Furthermore, LPS injection experiment indicated that the binding of EcC1INH N-terminal domain to LPS can antagonize LPS-induced inflammatory signaling pathway and attenuate the production of proinflammatory cytokines in vivo, indicating that EcC1INH was involved in negative regulation of inflammatory response.