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

Fish Shellfish Immunol. 2019 Jan:84:8-19. doi: 10.1016/j.fsi.2018.09.063. Epub 2018 Sep 24.

Abstract

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.

Keywords: C1INH; Cytokine expression; Inflammatory response; Mutagenesis.

MeSH terms

  • Animals
  • Complement C1 Inhibitor Protein* / genetics
  • Complement C1 Inhibitor Protein* / immunology
  • Fish Diseases / genetics
  • Fish Diseases / immunology
  • Fish Proteins* / genetics
  • Fish Proteins* / immunology
  • Lipopolysaccharides / pharmacology
  • Liver / metabolism
  • Perciformes* / genetics
  • Perciformes* / immunology
  • Protein Domains
  • Vibrio Infections / genetics
  • Vibrio Infections / immunology
  • Vibrio Infections / veterinary
  • Vibrio alginolyticus

Substances

  • Complement C1 Inhibitor Protein
  • Fish Proteins
  • Lipopolysaccharides