PMID- 31606893
OWN - NLM
STAT- MEDLINE
DCOM- 20200203
LR  - 20210101
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Print)
IS  - 0019-2805 (Linking)
VI  - 159
IP  - 1
DP  - 2020 Jan
TI  - The immunosuppressive functions of two novel tick serpins, HlSerpin-a and 
      HlSerpin-b, from Haemaphysalis longicornis.
PG  - 109-120
LID - 10.1111/imm.13130 [doi]
AB  - 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-alpha, 
      interleukin (IL)-6 and IL-1beta 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.
CI  - (c) 2019 John Wiley & Sons Ltd.
FAU - Wang, Fanqi
AU  - Wang F
AD  - Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection 
      and Immunity, Soochow University, Suzhou, China.
FAU - Song, Zhenyu
AU  - Song Z
AD  - Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection 
      and Immunity, Soochow University, Suzhou, China.
FAU - Chen, Jing
AU  - Chen J
AD  - NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood 
      Research), Fudan University, Shanghai, China.
FAU - Wu, Qihan
AU  - Wu Q
AD  - NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood 
      Research), Fudan University, Shanghai, China.
FAU - Zhou, Xia
AU  - Zhou X
AD  - School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China.
FAU - Ni, Xiaohua
AU  - Ni X
AD  - NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood 
      Research), Fudan University, Shanghai, China.
FAU - Dai, Jianfeng
AU  - Dai J
AUID- ORCID: 0000-0002-1871-8390
AD  - Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection 
      and Immunity, Soochow University, Suzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191110
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Arthropod Proteins)
RN  - 0 (Cytokines)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Serpins)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/immunology/metabolism/pathology/*prevention & control
MH  - Arthropod Proteins/genetics/isolation & purification/*pharmacology
MH  - Cytokines/metabolism
MH  - Dendritic Cells/*drug effects/immunology/metabolism
MH  - Immunosuppressive Agents/isolation & purification/*pharmacology
MH  - Ixodidae/genetics/*metabolism
MH  - Joints/*drug effects/immunology/metabolism/pathology
MH  - Macrophages/*drug effects/immunology/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred DBA
MH  - Protein Conformation
MH  - RAW 264.7 Cells
MH  - Saliva/metabolism
MH  - Serpins/genetics/isolation & purification/*pharmacology
MH  - Structure-Activity Relationship
PMC - PMC6904602
OTO - NOTNLM
OT  - activation
OT  - inflammation
OT  - regulation
OT  - suppression
COIS- The authors have declared that no conflict of interest exists.
EDAT- 2019/10/14 06:00
MHDA- 2020/02/06 06:00
PMCR- 2021/01/01
CRDT- 2019/10/14 06:00
PHST- 2019/09/04 00:00 [received]
PHST- 2019/10/07 00:00 [revised]
PHST- 2019/10/09 00:00 [accepted]
PHST- 2019/10/14 06:00 [pubmed]
PHST- 2020/02/06 06:00 [medline]
PHST- 2019/10/14 06:00 [entrez]
PHST- 2021/01/01 00:00 [pmc-release]
AID - IMM13130 [pii]
AID - 10.1111/imm.13130 [doi]
PST - ppublish
SO  - Immunology. 2020 Jan;159(1):109-120. doi: 10.1111/imm.13130. Epub 2019 Nov 10.