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The role of serpin protein on the natural immune defense against pathogen infection in Lampetra japonica.

Abstract

Serine protease inhibitors (serpins) are a large protein family that is involved in various physiological processes and is known to regulate innate immunity pathways. However, research for the functional study of serpins in lamprey is limited. In the present study, a serpin gene was cloned and characterized from Lampetra japonica at molecular, protein and cellular levels, named L-serpin which belongs to family F serine protease inhibitors (serpin family). The L-serpin includes a serpin domain in the N-terminus. The mRNA transcript of L-serpin was extensively expressed in kidney, supraneural body, intestine, liver, heart, gill and the highest expression in leukocytes. The mRNA expression level of L-serpin increased significantly after Vibrio anguillarum, Staphylocccus aureus and Poly I:C stimulation and dramatically peak at 8 h. It is demonstrated that the L-serpin protected cells from lethal Gram-negative endotoxemia through associating with inhibition of lipopolysaccharide (LPS)-triggered cell death and inflammatory factors expression. Surface plasmon resonance (SPR) and the microbe binding assay were used to determine that L-serpin interacts directly with LPS (KD = 6.14 × 10-7 M). Furthermore, we confirmed L-serpin is a major inhibitor of complement activation by inactivating lamprey-C1q protein (KD = 2.06 × 10-6 M). Taken together, these findings suggest that L-serpin is a endogenous anti-inflammatory factor to defend against Gram-negative bacterial challenge and involved in lamprey innate immunity.

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  • Authors+Show Affiliations

    ,

    College of Life Sciences, Liaoning Normal University, Dalian, 116081, China; Lamprey Research Center, Liaoning Normal University, Dalian, 116081, China. Electronic address: wangdayu0326@163.com.

    ,

    College of Life Sciences, Liaoning Normal University, Dalian, 116081, China; Lamprey Research Center, Liaoning Normal University, Dalian, 116081, China. Electronic address: gouer602@126.com.

    ,

    College of Life Sciences, Liaoning Normal University, Dalian, 116081, China; Lamprey Research Center, Liaoning Normal University, Dalian, 116081, China. Electronic address: hyjdu1025@163.com.

    ,

    College of Life Sciences, Liaoning Normal University, Dalian, 116081, China; Lamprey Research Center, Liaoning Normal University, Dalian, 116081, China. Electronic address: pangyue@lnnu.edu.cn.

    College of Life Sciences, Liaoning Normal University, Dalian, 116081, China; Lamprey Research Center, Liaoning Normal University, Dalian, 116081, China. Electronic address: liqw@lnnu.edu.cn.

    Source

    Fish & shellfish immunology 92: 2019 Jun 05 pg 196-208

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31176010

    Citation

    Wang, Dayu, et al. "The Role of Serpin Protein On the Natural Immune Defense Against Pathogen Infection in Lampetra Japonica." Fish & Shellfish Immunology, vol. 92, 2019, pp. 196-208.
    Wang D, Gou M, Hou J, et al. The role of serpin protein on the natural immune defense against pathogen infection in Lampetra japonica. Fish Shellfish Immunol. 2019;92:196-208.
    Wang, D., Gou, M., Hou, J., Pang, Y., & Li, Q. (2019). The role of serpin protein on the natural immune defense against pathogen infection in Lampetra japonica. Fish & Shellfish Immunology, 92, pp. 196-208. doi:10.1016/j.fsi.2019.05.062.
    Wang D, et al. The Role of Serpin Protein On the Natural Immune Defense Against Pathogen Infection in Lampetra Japonica. Fish Shellfish Immunol. 2019 Jun 5;92:196-208. PubMed PMID: 31176010.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - The role of serpin protein on the natural immune defense against pathogen infection in Lampetra japonica. AU - Wang,Dayu, AU - Gou,Meng, AU - Hou,Jianqiang, AU - Pang,Yue, AU - Li,Qingwei, Y1 - 2019/06/05/ PY - 2019/02/15/received PY - 2019/05/27/revised PY - 2019/05/30/accepted PY - 2019/6/9/pubmed PY - 2019/6/9/medline PY - 2019/6/9/entrez KW - Anti-inflammatory factor KW - C1q KW - Innate immunity KW - LPS binding KW - Lampetra japonica KW - Serpin SP - 196 EP - 208 JF - Fish & shellfish immunology JO - Fish Shellfish Immunol. VL - 92 N2 - Serine protease inhibitors (serpins) are a large protein family that is involved in various physiological processes and is known to regulate innate immunity pathways. However, research for the functional study of serpins in lamprey is limited. In the present study, a serpin gene was cloned and characterized from Lampetra japonica at molecular, protein and cellular levels, named L-serpin which belongs to family F serine protease inhibitors (serpin family). The L-serpin includes a serpin domain in the N-terminus. The mRNA transcript of L-serpin was extensively expressed in kidney, supraneural body, intestine, liver, heart, gill and the highest expression in leukocytes. The mRNA expression level of L-serpin increased significantly after Vibrio anguillarum, Staphylocccus aureus and Poly I:C stimulation and dramatically peak at 8 h. It is demonstrated that the L-serpin protected cells from lethal Gram-negative endotoxemia through associating with inhibition of lipopolysaccharide (LPS)-triggered cell death and inflammatory factors expression. Surface plasmon resonance (SPR) and the microbe binding assay were used to determine that L-serpin interacts directly with LPS (KD = 6.14 × 10-7 M). Furthermore, we confirmed L-serpin is a major inhibitor of complement activation by inactivating lamprey-C1q protein (KD = 2.06 × 10-6 M). Taken together, these findings suggest that L-serpin is a endogenous anti-inflammatory factor to defend against Gram-negative bacterial challenge and involved in lamprey innate immunity. SN - 1095-9947 UR - https://www.unboundmedicine.com/medline/citation/31176010/The_role_of_serpin_protein_on_the_natural_immune_defense_against_pathogen_infection_in_Lampetra_japonica L2 - https://linkinghub.elsevier.com/retrieve/pii/S1050-4648(19)30630-8 DB - PRIME DP - Unbound Medicine ER -