PMID- 37574155
OWN - NLM
STAT- Publisher
LR  - 20231013
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 196
DP  - 2023 Oct
TI  - Stabilization of activated mast cells by ORAI1 inhibitor suppresses 
      peanut-induced anaphylaxis and acute diarrhea.
PG  - 106887
LID - S1043-6618(23)00243-8 [pii]
LID - 10.1016/j.phrs.2023.106887 [doi]
AB  - Mast cell (MC) activation triggered by immunoglobulin E (IgE)-antigen 
      crosslinking involves intracellular Ca(2+) influx through the ORAI1 channel, 
      which precedes granule exteriorization and de novo synthesis of mediators. 
      Pharmacologically suppressing MCs via the inhibition of the ORAI1 Ca(2+) channel 
      may represent a potential strategy for preventing anaphylaxis. This study 
      demonstrated that peanut-induced anaphylaxis in sensitized mice resulted in 
      significant hypothermia and acute diarrhea. Utilizing the Mcpt5cre-DTA mouse 
      model, we demonstrated that this anaphylactic response was mediated by 
      IgE-antigen-induced MC activation. Prophylactic administration of MC suppressors 
      was an effective means of preventing peanut-induced anaphylaxis. In addition, we 
      observed the potent efficacy of an ORAI1 inhibitor in suppressing the 
      FcepsilonRI-mediated response of murine or human MCs, even when administered 
      concurrently or post-allergen exposure. Mechanistically, the ORAI1 inhibitor was 
      found to prevent the association of Synaptotagmin-2 with the SNARE complex. In an 
      in vivo mouse model of peanut-induced anaphylaxis, the administration of the 
      ORAI1 inhibitor after allergen challenge effectively suppressed allergic acute 
      diarrhea and ameliorated anaphylaxis. Therefore, pharmacological intervention of 
      ORAI1 channel inhibition in MCs represents a promising therapeutic avenue for the 
      treatment of peanut-induced anaphylaxis and acute diarrhea in vivo.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Suk, Gyeongseo
AU  - Suk G
AD  - Division of Life Sciences, Korea University, Seoul 02841, South Korea.
FAU - Kwon, Do Hoon
AU  - Kwon DH
AD  - Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, 
      USA.
FAU - Roers, Axel
AU  - Roers A
AD  - Institute for Immunology, Medical Faculty Carl Gustav Carus, Technische 
      Universitat Dresden, Dresden 01069, Germany.
FAU - Abraham, Soman N
AU  - Abraham SN
AD  - Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA; 
      Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA; 
      Molecular Genetics & Microbiology, Duke University Medical Center, Durham, NC 
      27710, USA.
FAU - Choi, Hae Woong
AU  - Choi HW
AD  - Division of Life Sciences, Korea University, Seoul 02841, South Korea. Electronic 
      address: haewoongchoi@korea.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20230811
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
SB  - IM
OTO - NOTNLM
OT  - Allergy
OT  - Anaphylaxis
OT  - Mast cell
OT  - ORAI1 inhibitor
COIS- Declaration of Competing Interest None.
EDAT- 2023/08/14 00:43
MHDA- 2023/08/14 00:43
CRDT- 2023/08/13 19:27
PHST- 2023/03/06 00:00 [received]
PHST- 2023/08/10 00:00 [revised]
PHST- 2023/08/10 00:00 [accepted]
PHST- 2023/08/14 00:43 [pubmed]
PHST- 2023/08/14 00:43 [medline]
PHST- 2023/08/13 19:27 [entrez]
AID - S1043-6618(23)00243-8 [pii]
AID - 10.1016/j.phrs.2023.106887 [doi]
PST - ppublish
SO  - Pharmacol Res. 2023 Oct;196:106887. doi: 10.1016/j.phrs.2023.106887. Epub 2023 
      Aug 11.