PMID- 35592412
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220521
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Dihydroarteannuin Ameliorates Collagen-Induced Arthritis Via Inhibiting B Cell 
      Activation by Activating the FcgammaRIIb/Lyn/SHP-1 Pathway.
PG  - 883835
LID - 10.3389/fphar.2022.883835 [doi]
LID - 883835
AB  - Background: Dihydroarteannuin (DHA), which is extracted from the traditional 
      Chinese herb Artemisia annua L, exhibits potent immunosuppressive activity in 
      rheumatoid arthritis (RA). Strong evidence indicates that B cells act as an 
      essential factor in the pathogenesis of RA, but research on the immunosuppressive 
      function of DHA in regulating B cells is limited. Objective: To investigate the 
      modulatory effects of DHA on joint destruction, proinflammatory cytokine 
      production, activation, apoptosis and proliferation of B cells and to explore the 
      possible associated mechanism in RA treatment. Methods: Collagen-induced 
      arthritis (CIA) model was established. Weight and joint oedema were record 
      weekly, and joint damage was detected by micro-CT scan. Human Burkitt B lymphoma 
      cells lacking endogenous Fc gamma receptor b (FcgammaRIIb) gene were transfected with 
      a 232Thr loss-of-function mutant to construct a mutant cell model ST486. The 
      proliferation of ST486 cells was assessed with Cell Counting Kit-8. Apoptosis and 
      activation were tested by flow cytometry. The effects of DHA on the activation of 
      FcgammaRIIb, protein tyrosine kinases (Lyn), and SH2-containing tyrosine 
      phosphatase-1 (SHP-1) signaling pathways were determined by western blotting. 
      Results: In comparison to model group, bone volume/tissue volume (BV/TV) and bone 
      mineral density (BMD) were increased, whereas joint oedema was decreased in both 
      of the DHA and MTX group. The mRNA and protein expression levels of Interleukin-6 
      (IL-6) and Tumor necrosis factor-alpha (TNF-alpha) were decreased after treatment 
      with DHA. In addition, DHA treatment promoted the apoptosis, inhibited the 
      activation and proliferation of ST486 cells. Furthermore, the protein expression 
      levels of FcgammaRIIb, SHP-1, and Lyn were increased after treatment with DHA. 
      Moreover, the expression of phosphorylated CD19 was also inhibited by DHA. 
      Conclusion: We provide the first evidence that DHA may alleviate collagen-induced 
      arthritis by activating the FcgammaRIIb/Lyn/SHP-1 signaling pathway in B cell, 
      indicating that DHA is a novel and valuable candidate for RA therapy.
CI  - Copyright (c) 2022 Hu, Wu, Yu, Xu, Liu, Zhang, Jiao and Chen.
FAU - Hu, Congqi
AU  - Hu C
AD  - First Clinical Medical School, Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
AD  - Department of Rheumatology, The First Affiliated Hospital of Guangzhou University 
      of Chinese Medicine, Guangzhou, China.
FAU - Wu, Danbin
AU  - Wu D
AD  - First Clinical Medical School, Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
AD  - Department of Rheumatology, The First Affiliated Hospital of Guangzhou University 
      of Chinese Medicine, Guangzhou, China.
FAU - Yu, Jiahui
AU  - Yu J
AD  - First Clinical Medical School, Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
AD  - Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
FAU - Xu, Jia
AU  - Xu J
AD  - First Clinical Medical School, Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
AD  - Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
FAU - Liu, Lijuan
AU  - Liu L
AD  - First Clinical Medical School, Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
AD  - Department of Rheumatology, The First Affiliated Hospital of Guangzhou University 
      of Chinese Medicine, Guangzhou, China.
FAU - Zhang, Mingying
AU  - Zhang M
AD  - First Clinical Medical School, Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
AD  - Department of Rheumatology, The First Affiliated Hospital of Guangzhou University 
      of Chinese Medicine, Guangzhou, China.
FAU - Jiao, Wei
AU  - Jiao W
AD  - First Clinical Medical School, Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
AD  - Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
FAU - Chen, Guangxing
AU  - Chen G
AD  - Department of Rheumatology, The First Affiliated Hospital of Guangzhou University 
      of Chinese Medicine, Guangzhou, China.
AD  - Baiyun Hospital of The First Affiliated Hospital of Guangzhou University of 
      Chinese Medicine, Guangzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20220503
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9111742
OTO - NOTNLM
OT  - CIA mice
OT  - FcgammaRIIb
OT  - ST486
OT  - dihydroarteannuin
OT  - rheumatoid arthritis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/05/21 06:00
MHDA- 2022/05/21 06:01
PMCR- 2022/05/03
CRDT- 2022/05/20 02:24
PHST- 2022/02/25 00:00 [received]
PHST- 2022/04/20 00:00 [accepted]
PHST- 2022/05/20 02:24 [entrez]
PHST- 2022/05/21 06:00 [pubmed]
PHST- 2022/05/21 06:01 [medline]
PHST- 2022/05/03 00:00 [pmc-release]
AID - 883835 [pii]
AID - 10.3389/fphar.2022.883835 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 May 3;13:883835. doi: 10.3389/fphar.2022.883835. 
      eCollection 2022.