Stabilization of activated mast cells by ORAI1 inhibitor suppresses peanut-induced anaphylaxis and acute diarrhea Article Swipe
Gyeongseo Suk
,
Do Hoon Kwon
,
Axel Roers
,
Soman N. Abraham
,
Hae Woong Choi
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1016/j.phrs.2023.106887
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1016/j.phrs.2023.106887
Mast cell (MC) activation triggered by immunoglobulin E (IgE)-antigen crosslinking involves intracellular Ca2+ influx through the ORAI1 channel, which precedes granule exteriorization and de novo synthesis of mediators. Pharmacologically suppressing MCs via the inhibition of the ORAI1 Ca2+ 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 FcεRI-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.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.phrs.2023.106887
- OA Status
- gold
- Cited By
- 1
- References
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- Related Works
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- OpenAlex ID
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All OpenAlex metadata
Raw OpenAlex JSON
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https://openalex.org/W4385765493Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1016/j.phrs.2023.106887Digital Object Identifier
- Title
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Stabilization of activated mast cells by ORAI1 inhibitor suppresses peanut-induced anaphylaxis and acute diarrheaWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-08-11Full publication date if available
- Authors
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Gyeongseo Suk, Do Hoon Kwon, Axel Roers, Soman N. Abraham, Hae Woong ChoiList of authors in order
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https://doi.org/10.1016/j.phrs.2023.106887Publisher landing page
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
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https://doi.org/10.1016/j.phrs.2023.106887Direct OA link when available
- Concepts
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Anaphylaxis, Immunoglobulin E, Pharmacology, Medicine, Immunology, In vivo, Allergy, Antibody, Biology, BiotechnologyTop concepts (fields/topics) attached by OpenAlex
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1Total citation count in OpenAlex
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2024: 1Per-year citation counts (last 5 years)
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10Other works algorithmically related by OpenAlex
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