The immunosuppressive functions of two novel tick serpins, HlSerpin-a and HlSerpin-b, from Haemaphysalis longicornis.
Serpins are evolutionarily conserved serine protease inhibitors that are widely distributed in animals, plants and microbes. In this study, we reported the cloning and functional characterizations of two novel serpin genes, HlSerpin-a and HlSerpin-b, from the hard tick Haemaphysalis longicornis of China. Recombinant HlSerpin-a and HlSerpin-b displayed protease inhibitory activities against multiple mammalian proteases. Similar to other tick serpins, HlSerpin-a and HlSerpin-b suppressed the expression of inflammatory cytokines such as TNF-α, interleukin (IL)-6 and IL-1β from lipopolysaccharide-stimulated mouse bone-marrow-derived macrophages (BMDMs) or mouse bone-marrow-derived dendritic cells (BMDCs). The minimum active region (reaction centre loop) of HlSerpin-a, named SA-RCL, showed similar biological activities as HlSerpin-a in the protease inhibition and immune suppression assays. The immunosuppressive activities of full-length HlSerpin-a and SA-RCL are impaired in Cathepsin G or Cathepsin B knockout mouse macrophages, suggesting that the immunomodulation functions of SA and SA-RCL are dependent on their protease inhibitory activity. Finally, we showed that both full-length HlSerpins and SA-RCL can relieve the joint swelling and inflammatory response in collagen-induced mouse arthritis models. These results suggested that HlSerpin-a and HlSerpin-b are two functional arthropod serpins, and the minimal reactive peptide SA-RCL is a potential candidate for drug development against inflammatory diseases.
['Wang|Fanqi|F|', 'Song|Zhenyu|Z|', 'Chen|Jing|J|', 'Wu|Qihan|Q|', 'Zhou|Xia|X|', 'Ni|Xiaohua|X|', 'Dai|Jianfeng|J|0000-0002-1871-8390']
D000818:Animals D001169:Arthritis, Experimental D060829:Arthropod Proteins D016207:Cytokines D003713:Dendritic Cells D007166:Immunosuppressive Agents D026863:Ixodidae D007596:Joints D008264:Macrophages D008297:Male D051379:Mice D008811:Mice, Inbred DBA D011487:Protein Conformation D000067996:RAW 264.7 Cells D012463:Saliva D015843:Serpins D013329:Structure-Activity Relationship
activation suppression inflammation regulation