PMID- 30771056
OWN - NLM
STAT- MEDLINE
DCOM- 20191127
LR  - 20220720
IS  - 1568-5608 (Electronic)
IS  - 0925-4692 (Linking)
VI  - 27
IP  - 5
DP  - 2019 Oct
TI  - Regulatory effects of paeoniflorin-6'-O-benzene sulfonate (CP-25) on dendritic 
      cells maturation and activation via PGE2-EP4 signaling in adjuvant-induced 
      arthritic rats.
PG  - 997-1010
LID - 10.1007/s10787-019-00575-8 [doi]
AB  - Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease. Dendritic 
      cells (DCs) are one of the most powerful antigen-presenting cells, and they play 
      an important role in RA pathogenesis. Prostaglandin E2 (PGE2) is a potent lipid 
      mediator that can regulate the maturation and activation of DCs, but the 
      molecular mechanisms have not been elucidated. In this study, both in vitro and 
      in an RA rat model, we investigated the mechanisms involved by focusing on 
      PGE2-mediated signaling and using a novel anti-inflammatory compound, 
      paeoniflorin-6'-O-benzene sulfonate (CP-25). PGE2 combined with tumor necrosis 
      factor-alpha promoted DC maturation and activation through EP4-cAMP signaling. 
      Treatment with CP-25 increased the endocytic capacity of DCs induced by PGE2. 
      CP-25 inhibited the potency of DCs induced by the EP4 receptor agonist, CAY10598, 
      to stimulate allogeneic T cells. Consistent with these findings, the 
      CAY10598-induced upregulation of DC surface activation markers and production of 
      IL-23 was significantly inhibited by CP-25 in a concentration-dependent manner. 
      In vivo administration of CP-25 alleviated adjuvant arthritis (AA) in rats 
      through inhibition of DC maturation and activation. Our results indicate that 
      PGE2-EP4-cAMP signal hyperfunction can lead to abnormal activation of DC 
      functions, which correlates with the course of disease in AA rats and provides a 
      possible treatment target. The inhibition of DC maturation and activation by 
      CP-25 interference of the PGE2-EP4 pathway may significantly contribute to the 
      immunoregulatory profile of CP-25 when used to treat RA and other immune 
      cell-mediated disorders.
FAU - Jia, Xiao-Yi
AU  - Jia XY
AD  - Institute of Clinical Pharmacology, Key Laboratory of Anti-Inflammatory and 
      Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of 
      Anti-Inflammatory and Immune Medicine, Anhui Medical University, 81 Meishan Road, 
      Hefei, 230032, China.
AD  - School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China.
FAU - Chang, Yan
AU  - Chang Y
AD  - Institute of Clinical Pharmacology, Key Laboratory of Anti-Inflammatory and 
      Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of 
      Anti-Inflammatory and Immune Medicine, Anhui Medical University, 81 Meishan Road, 
      Hefei, 230032, China.
FAU - Sun, Xiao-Jing
AU  - Sun XJ
AD  - Institute of Clinical Pharmacology, Key Laboratory of Anti-Inflammatory and 
      Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of 
      Anti-Inflammatory and Immune Medicine, Anhui Medical University, 81 Meishan Road, 
      Hefei, 230032, China.
FAU - Wei, Fang
AU  - Wei F
AD  - Institute of Clinical Pharmacology, Key Laboratory of Anti-Inflammatory and 
      Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of 
      Anti-Inflammatory and Immune Medicine, Anhui Medical University, 81 Meishan Road, 
      Hefei, 230032, China.
FAU - Wu, Yu-Jing
AU  - Wu YJ
AD  - Institute of Clinical Pharmacology, Key Laboratory of Anti-Inflammatory and 
      Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of 
      Anti-Inflammatory and Immune Medicine, Anhui Medical University, 81 Meishan Road, 
      Hefei, 230032, China.
FAU - Dai, Xing
AU  - Dai X
AD  - Institute of Clinical Pharmacology, Key Laboratory of Anti-Inflammatory and 
      Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of 
      Anti-Inflammatory and Immune Medicine, Anhui Medical University, 81 Meishan Road, 
      Hefei, 230032, China.
FAU - Xu, Shu
AU  - Xu S
AD  - Institute of Clinical Pharmacology, Key Laboratory of Anti-Inflammatory and 
      Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of 
      Anti-Inflammatory and Immune Medicine, Anhui Medical University, 81 Meishan Road, 
      Hefei, 230032, China.
FAU - Wu, Hua-Xun
AU  - Wu HX
AD  - Institute of Clinical Pharmacology, Key Laboratory of Anti-Inflammatory and 
      Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of 
      Anti-Inflammatory and Immune Medicine, Anhui Medical University, 81 Meishan Road, 
      Hefei, 230032, China.
FAU - Wang, Chun
AU  - Wang C
AD  - Institute of Clinical Pharmacology, Key Laboratory of Anti-Inflammatory and 
      Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of 
      Anti-Inflammatory and Immune Medicine, Anhui Medical University, 81 Meishan Road, 
      Hefei, 230032, China.
FAU - Yang, Xue-Zhi
AU  - Yang XZ
AD  - Institute of Clinical Pharmacology, Key Laboratory of Anti-Inflammatory and 
      Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of 
      Anti-Inflammatory and Immune Medicine, Anhui Medical University, 81 Meishan Road, 
      Hefei, 230032, China.
FAU - Wei, Wei
AU  - Wei W
AD  - Institute of Clinical Pharmacology, Key Laboratory of Anti-Inflammatory and 
      Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of 
      Anti-Inflammatory and Immune Medicine, Anhui Medical University, 81 Meishan Road, 
      Hefei, 230032, China. wwei@ahmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20190215
PL  - Switzerland
TA  - Inflammopharmacology
JT  - Inflammopharmacology
JID - 9112626
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Adjuvants, Pharmaceutic)
RN  - 0 (Glucosides)
RN  - 0 (Monoterpenes)
RN  - 0 (Receptors, Prostaglandin E, EP4 Subtype)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (paeoniflorin-6'-O-benzenesulfonate)
RN  - E0399OZS9N (Cyclic AMP)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Adjuvants, Immunologic/*adverse effects
MH  - Adjuvants, Pharmaceutic/adverse effects
MH  - Animals
MH  - Arthritis, Experimental/chemically induced/*drug therapy/metabolism
MH  - Arthritis, Rheumatoid/chemically induced/drug therapy/metabolism
MH  - Cyclic AMP/metabolism
MH  - Dendritic Cells/*drug effects/metabolism
MH  - Dinoprostone/*metabolism
MH  - Glucosides/*pharmacology
MH  - Male
MH  - Monoterpenes/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Prostaglandin E, EP4 Subtype/*metabolism
MH  - Signal Transduction/*drug effects
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - Adjuvant-induced arthritis
OT  - Dendritic cell
OT  - EP receptor
OT  - PGE2
OT  - Paeoniflorin-6'-O-benzene sulfonate
OT  - cAMP
EDAT- 2019/02/17 06:00
MHDA- 2019/11/28 06:00
CRDT- 2019/02/17 06:00
PHST- 2018/10/24 00:00 [received]
PHST- 2019/02/05 00:00 [accepted]
PHST- 2019/02/17 06:00 [pubmed]
PHST- 2019/11/28 06:00 [medline]
PHST- 2019/02/17 06:00 [entrez]
AID - 10.1007/s10787-019-00575-8 [pii]
AID - 10.1007/s10787-019-00575-8 [doi]
PST - ppublish
SO  - Inflammopharmacology. 2019 Oct;27(5):997-1010. doi: 10.1007/s10787-019-00575-8. 
      Epub 2019 Feb 15.