PMID- 37454634
OWN - NLM
STAT- MEDLINE
DCOM- 20230825
LR  - 20230825
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 122
DP  - 2023 Sep
TI  - Taurodeoxycholate ameliorates DSS-induced colitis in mice.
PG  - 110628
LID - S1567-5769(23)00953-0 [pii]
LID - 10.1016/j.intimp.2023.110628 [doi]
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is typically managed using 
      medications such as 5-aminosalicylic acid (5-ASA), glucocorticoids, anti-TNFalpha Ab, 
      or anti-IL-12/23 Ab. However, some patients do not respond well to these 
      treatments or frequently experience relapses. Therefore, alternative therapeutic 
      options are needed. Since the activation of the inflammasome is crucial to the 
      pathogenesis of IBD, inhibiting the inflammasome may be beneficial for patients. 
      MATERIALS AND METHODS: We tested the efficacy of taurodeoxycholate (TDCA), which 
      is a known G-protein coupled receptor 19 (GPCR19) agonist, in a mouse colitis 
      model induced by dextran sodium sulfate (DSS). RESULTS: In the mouse colitis 
      model, TDCA prevented loss of body weight, shortening of the colon, production of 
      pro-inflammatory cytokines, infiltration of pro-inflammatory cells, and mucosal 
      ulceration in the colon. In vitro, TDCA inhibited the activation of NF-kappaB in bone 
      marrow-derived macrophages (BMDMs) by activating the cAMP-PKA axis. TDCA 
      downregulated the expression of purinergic receptor P2X7 (P2X7R) and enhanced the 
      colocalization of P2X7R with GPCR19, and inhibited the Ca(2+) mobilization of 
      BMDMs when stimulated with ATP or BzATP, which plays a pivotal role in activating 
      the NLRP3 inflammasome (N3I) via P2X7R. TDCA inhibited the oligomerization of 
      NLRP3-ASC and downregulated the expression of NLRP3 and ASC, as well as 
      suppressed the maturation of pro-caspase-1 and pro-IL-1beta. TDCA also increased the 
      percentage of M2 macrophages while decreasing the number of M1 macrophages, Th1, 
      Th2, and Th17 cells in the colon. CONCLUSION: TDCA ameliorated DSS-induced 
      colitis in mice, possibly by inhibiting both the priming phase (via the 
      GPCR19-cAMP-PKA-NF-kappaB axis) and the activation phase (via the 
      GPCR19-P2X7R-NLRP3-Caspase 1-IL-1beta axis) of N3I signaling.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Zou, Yunyun
AU  - Zou Y
AD  - Wide River Institute of Immunology, Seoul National University, Hongcheon, 
      Republic of Korea; Department of Biomedical Sciences, Seoul National University 
      College of Medicine, Seoul, Republic of Korea.
FAU - Ghaderpour, Aziz
AU  - Ghaderpour A
AD  - Wide River Institute of Immunology, Seoul National University, Hongcheon, 
      Republic of Korea; Department of Biomedical Sciences, Seoul National University 
      College of Medicine, Seoul, Republic of Korea.
FAU - Munkhbileg, Bolormaa
AU  - Munkhbileg B
AD  - Wide River Institute of Immunology, Seoul National University, Hongcheon, 
      Republic of Korea; Department of Microbiology and Immunology, Seoul National 
      University College of Medicine, Seoul, Republic of Korea.
FAU - Seo, Sang-Uk
AU  - Seo SU
AD  - Department of Microbiology, College of Medicine, The Catholic University of 
      Korea, Seoul, Republic of Korea.
FAU - Seong, Seung-Yong
AU  - Seong SY
AD  - Wide River Institute of Immunology, Seoul National University, Hongcheon, 
      Republic of Korea; Department of Biomedical Sciences, Seoul National University 
      College of Medicine, Seoul, Republic of Korea; Department of Microbiology and 
      Immunology, Seoul National University College of Medicine, Seoul, Republic of 
      Korea; Shaperon Inc., Seoul, Republic of Korea. Electronic address: 
      seongsy@snu.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20230714
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (NF-kappa B)
RN  - 9042-14-2 (Dextran Sulfate)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Inflammasomes/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - NF-kappa B/metabolism
MH  - *Colitis/chemically induced/drug therapy/metabolism
MH  - *Inflammatory Bowel Diseases/metabolism
MH  - Dextran Sulfate
MH  - Mice, Inbred C57BL
OTO - NOTNLM
OT  - GPCR19
OT  - NLRP3
OT  - P2X7R
OT  - TDCA
OT  - Ulcerative colitis
COIS- Declaration of Competing Interest The patent titled "Composition Comprising 
      GPCR19 Agonist as an Active Ingredient for Preventing or Treating Inflammatory 
      Bowel Disease" with the following references: KR102204406B1, PCT/KR2020/001179, 
      17/284.305, 202080005732.3, 2021-547027, 20745833.2, 202147022375, was invented 
      by Seong et al. and applied for by the Seoul National University R&DB Foundation. 
      The exclusive license for the patent was transferred from SNU R&DB to Shaperon 
      Inc., of which Dr. S.Y. Seong is a founder and the current CEO. The other authors 
      declare that they have no known competing financial interests or personal 
      relationships that could have appeared to influence the work reported in this 
      paper.
EDAT- 2023/07/17 00:42
MHDA- 2023/08/25 06:42
CRDT- 2023/07/16 18:09
PHST- 2023/04/16 00:00 [received]
PHST- 2023/07/04 00:00 [revised]
PHST- 2023/07/06 00:00 [accepted]
PHST- 2023/08/25 06:42 [medline]
PHST- 2023/07/17 00:42 [pubmed]
PHST- 2023/07/16 18:09 [entrez]
AID - S1567-5769(23)00953-0 [pii]
AID - 10.1016/j.intimp.2023.110628 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2023 Sep;122:110628. doi: 10.1016/j.intimp.2023.110628. Epub 
      2023 Jul 14.