PMID- 31722050
OWN - NLM
STAT- MEDLINE
DCOM- 20201228
LR  - 20201228
IS  - 1573-6830 (Electronic)
IS  - 0272-4340 (Linking)
VI  - 40
IP  - 4
DP  - 2020 May
TI  - Annexin-1 Mimetic Peptide Ac2-26 Suppresses Inflammatory Mediators in LPS-Induced 
      Astrocytes and Ameliorates Pain Hypersensitivity in a Rat Model of Inflammatory 
      Pain.
PG  - 569-585
LID - 10.1007/s10571-019-00755-8 [doi]
AB  - Ac2-26, a mimetic peptide of Annexin-A1, plays a vital role in the 
      anti-inflammatory response mediated by astrocytes. In this study, we aimed to 
      explore the underlying mechanisms of Ac2-26-mediated anti-inflammatory effect. 
      Specifically, we investigated the inhibitory effects of Ac2-26 on 
      lipopolysaccharide (LPS)-induced astrocyte migration and on pro-inflammatory 
      cytokines and chemokines expressions, as well as one glutathione (GSH) reductase 
      mRNA and total intracellular GSH levels in LPS-induced astrocytes. Additionally, 
      we investigated whether mitogen-activated protein kinases (MAPK) and nuclear 
      factor kappa-B (NF-kappaB) signaling pathway were involved in this process. Finally, 
      we evaluated the analgesic effect of Ac2-26 in complete Freund's adjuvant 
      (CFA)-induced inflammatory pain model. Our results demonstrated that Ac2-26 
      inhibited LPS-induced astrocytes migration, reduced the production of 
      pro-inflammatory mediators [tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta 
      (IL-1beta), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory 
      protein-1 (MIP-1alpha)] and upregulated GSH reductase mRNA and GSH levels in 
      LPS-induced astrocytes in vitro. This process was mediated through the p38, 
      JNK-MAPK signaling pathway, but not dependent on the NF-kappaB pathway. Furthermore, 
      the p38 and JNK inhibitors mimicked the effects of Ac2-26, whereas a p38 and JNK 
      activator anisomycin partially reversed its function. Finally, Ac2-26 treatment 
      reduced CFA-induced activation of astrocytes and production of inflammatory 
      mediators in the spinal cord. These results suggest that Ac2-26 attenuates pain 
      by inhibiting astrocyte activation and the production of inflammatory mediators; 
      thus, this work presents Ac2-26 as a potential drug to treat neuropathic pain.
FAU - Luo, Zhenzhao
AU  - Luo Z
AD  - Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical 
      College, Huazhong University of Science and Technology, 26 Shengli St., Jiangan 
      District, Wuhan, 430014, China.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical 
      College, Huazhong University of Science and Technology, 26 Shengli St., Jiangan 
      District, Wuhan, 430014, China.
FAU - Fang, Shiqiang
AU  - Fang S
AD  - Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical 
      College, Huazhong University of Science and Technology, 26 Shengli St., Jiangan 
      District, Wuhan, 430014, China.
FAU - Li, Li
AU  - Li L
AD  - Department of Pathology, The Central Hospital of Wuhan, Tongji Medical College, 
      Huazhong University of Science and Technology, 26 Shengli St., Jiangan District, 
      Wuhan, 430014, China.
FAU - Li, Xing
AU  - Li X
AD  - Department of Neurobiology, The School of Basic Medical Science, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, 430030, China.
FAU - Shi, Jing
AU  - Shi J
AD  - Department of Neurobiology, The School of Basic Medical Science, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, 430030, China.
FAU - Zhu, Man
AU  - Zhu M
AD  - Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical 
      College, Huazhong University of Science and Technology, 26 Shengli St., Jiangan 
      District, Wuhan, 430014, China.
FAU - Tan, Zheqiong
AU  - Tan Z
AD  - Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical 
      College, Huazhong University of Science and Technology, 26 Shengli St., Jiangan 
      District, Wuhan, 430014, China.
FAU - Lu, Zhongxin
AU  - Lu Z
AD  - Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical 
      College, Huazhong University of Science and Technology, 26 Shengli St., Jiangan 
      District, Wuhan, 430014, China. lzx71@yahoo.com.
LA  - eng
GR  - WX17Q10/Excellent Youth Foundation of Health and Family Planning Commission of 
      Wuhan Municipality/
GR  - 2016KF004/Open Research Fund Program of the State Key Laboratory of Virology of 
      China/
GR  - WJ2015MB144/Research Fund of Hubei Province Public Health Bureau/
GR  - WX15A12/Research Fund of Wuhan Public Health Bureau/
PT  - Journal Article
DEP - 20191113
PL  - United States
TA  - Cell Mol Neurobiol
JT  - Cellular and molecular neurobiology
JID - 8200709
RN  - 0 (Annexins)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Peptides)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Annexins/*chemistry
MH  - Astrocytes/metabolism/*pathology
MH  - Disease Models, Animal
MH  - Hyperalgesia/complications/drug therapy
MH  - Inflammation/complications/*drug therapy
MH  - Inflammation Mediators/*metabolism
MH  - Lipopolysaccharides
MH  - Male
MH  - Pain/complications/*drug therapy
MH  - Peptides/chemistry/pharmacology/*therapeutic use
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - Ac2-26
OT  - Annexin-1
OT  - GSH
OT  - Inflammatory mediators
OT  - MAPK pathway
OT  - Migration
EDAT- 2019/11/14 06:00
MHDA- 2020/12/29 06:00
CRDT- 2019/11/14 06:00
PHST- 2019/02/20 00:00 [received]
PHST- 2019/10/31 00:00 [accepted]
PHST- 2019/11/14 06:00 [pubmed]
PHST- 2020/12/29 06:00 [medline]
PHST- 2019/11/14 06:00 [entrez]
AID - 10.1007/s10571-019-00755-8 [pii]
AID - 10.1007/s10571-019-00755-8 [doi]
PST - ppublish
SO  - Cell Mol Neurobiol. 2020 May;40(4):569-585. doi: 10.1007/s10571-019-00755-8. Epub 
      2019 Nov 13.