Roles of TRPM4 in immune responses in keratinocytes and identification of a novel TRPM4-activating agent

Saito, Kaori Otsuka; Fujita, Fumitaka; Toriyama, Manami; Utami, Ratna Annisa; Guo, Zhihan; Murakami, Masato; Kato, Hiroko; Suzuki, Yoshiro; Okada, Fumihiro; Tominaga, Makoto; Ishii, Ken J.

doi:https://doi.org/10.1016/j.bbrc.2023.02.062

Roles of TRPM4 in immune responses in keratinocytes and identification of a novel TRPM4-activating agent

Saito, Kaori Otsuka; Fujita, Fumitaka; Toriyama, Manami et al.

Biochemical and Biophysical Research Communications, 2023, 654, 1-9

Number of Access:1,185（2025-08-21 07:02 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/91336

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Title	Roles of TRPM4 in immune responses in keratinocytes and identification of a novel TRPM4-activating agent
Creator	NRID 1000080836924 1000080836924 researchmap permalink kaosai kaosai CreatorName Saito, Kaori Otsuka
	CreatorName Fujita, Fumitaka
	NRID 1000030773121 1000030773121 CreatorName Toriyama, Manami
	CreatorName Utami, Ratna Annisa
	CreatorName Guo, Zhihan
	CreatorName Murakami, Masato
	NRID 1000070749994 1000070749994 ORCID 0000-0002-2618-5539 0000-0002-2618-5539 researchmap permalink hirokokato hirokokato Scopus Author ID 55314208200 55314208200 CreatorName Kato, Hiroko
	NRID 1000040348503 1000040348503 CreatorName Suzuki, Yoshiro
	CreatorName Okada, Fumihiro
	NRID 1000090260041 1000090260041 CreatorName Tominaga, Makoto
	NRID 1000000448086 1000000448086 CreatorName Ishii, Ken J.
Subject	Aluminum compounds
	Cytokines
	Inflammation
	Keratinocytes
	Skin
	Transient receptor potential melastatin 4 channel
Abstract	The skin is a protective interface between the internal organs and environment and functions not only as a physical barrier but also as an immune organ. However, the immune system in the skin is not fully understood. A member of the thermo-sensitive transient receptor potential (TRP) channel family, TRPM4, which acts as a regulatory receptor in immune cells, was recently reported to be expressed in human skin and keratinocytes. However, the function of TRPM4 in immune responses in keratinocytes has not been investigated. In this study, we found that treatment with BTP2, a known TRPM4 agonist, reduced cytokine production induced by tumor necrosis factor (TNF) α in normal human epidermal keratinocytes and in immortalized human epidermal keratinocytes (HaCaT cells). This cytokine-reducing effect was not observed in TRPM4-deficient HaCaT cells, indicating that TRPM4 contributed to the control of cytokine production in keratinocytes. Furthermore, we identified aluminum potassium sulfate, as a new TRPM4 activating agent. Aluminum potassium sulfate reduced Ca2+ influx by store-operated Ca2+ entry in human TRPM4-expressing HEK293T cells. We further confirmed that aluminum potassium sulfate evoked TRPM4-mediated currents, showing direct evidence for TRPM4 activation. Moreover, treatment with aluminum potassium sulfate reduced cytokine expression induced by TNFα in HaCaT cells. Taken together, our data suggested that TRPM4 may serve as a new target for the treatment of skin inflammatory reactions by suppressing the cytokine production in keratinocytes, and aluminum potassium sulfate is a useful ingredient to prevent undesirable skin inflammation through TRPM4 activation.
Publisher	Elsevier B.V.
Source Title	Biochemical and Biophysical Research Communications
Volume (Issue)	654
Page	1-9
Date of Issued	2023-03-03
Language	English
Handle URL	https://hdl.handle.net/11094/91336
PISSN	0006291X
eISSN	10902104
NCID	AA00564395
Relation.isVersionOf	DOI (Publisher Version) https://doi.org/10.1016/j.bbrc.2023.02.062
Access Rights	open access
CopyRight	© 2023. This manuscript version is made available under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
oaire:version	Accepted Manuscript
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Biochemical and Biophysical Research Communications. 2023, 654, p. 1-9
DC.title	Roles of TRPM4 in immune responses in keratinocytes and identification of a novel TRPM4-activating agent
DC.creator	Saito, Kaori Otsuka
	Fujita, Fumitaka
	Toriyama, Manami
	Utami, Ratna Annisa
	Guo, Zhihan
	Murakami, Masato
	Kato, Hiroko
	Suzuki, Yoshiro
	Okada, Fumihiro
	Tominaga, Makoto
	Ishii, Ken J.
DC.publisher	Elsevier B.V.
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2023-03-03
DC.identifier	https://doi.org/10.1016/j.bbrc.2023.02.062
DC.subject	Aluminum compounds
	Cytokines
	Inflammation
	Keratinocytes
	Skin
	Transient receptor potential melastatin 4 channel
DCTERMS.abstract	The skin is a protective interface between the internal organs and environment and functions not only as a physical barrier but also as an immune organ. However, the immune system in the skin is not fully understood. A member of the thermo-sensitive transient receptor potential (TRP) channel family, TRPM4, which acts as a regulatory receptor in immune cells, was recently reported to be expressed in human skin and keratinocytes. However, the function of TRPM4 in immune responses in keratinocytes has not been investigated. In this study, we found that treatment with BTP2, a known TRPM4 agonist, reduced cytokine production induced by tumor necrosis factor (TNF) α in normal human epidermal keratinocytes and in immortalized human epidermal keratinocytes (HaCaT cells). This cytokine-reducing effect was not observed in TRPM4-deficient HaCaT cells, indicating that TRPM4 contributed to the control of cytokine production in keratinocytes. Furthermore, we identified aluminum potassium sulfate, as a new TRPM4 activating agent. Aluminum potassium sulfate reduced Ca2+ influx by store-operated Ca2+ entry in human TRPM4-expressing HEK293T cells. We further confirmed that aluminum potassium sulfate evoked TRPM4-mediated currents, showing direct evidence for TRPM4 activation. Moreover, treatment with aluminum potassium sulfate reduced cytokine expression induced by TNFα in HaCaT cells. Taken together, our data suggested that TRPM4 may serve as a new target for the treatment of skin inflammatory reactions by suppressing the cytokine production in keratinocytes, and aluminum potassium sulfate is a useful ingredient to prevent undesirable skin inflammation through TRPM4 activation.
DC.rights	© 2023. This manuscript version is made available under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	91336
citation_title	Roles of TRPM4 in immune responses in keratinocytes and identification of a novel TRPM4-activating agent
citation_author	Saito, Kaori Otsuka
	Fujita, Fumitaka
	Toriyama, Manami
	Utami, Ratna Annisa
	Guo, Zhihan
	Murakami, Masato
	Kato, Hiroko
	Suzuki, Yoshiro
	Okada, Fumihiro
	Tominaga, Makoto
	Ishii, Ken J.
citation_publisher	Elsevier B.V.
citation_language	English
citation_date	2023-03-03
citation_journal_title	Biochemical and Biophysical Research Communications
citation_volume	654
citation_firstpage	1
citation_lastpage	9
citation_doi	https://doi.org/10.1016/j.bbrc.2023.02.062
citation_public_url	https://hdl.handle.net/11094/91336

Roles of TRPM4 in immune responses in keratinocytes and identification of a novel TRPM4-activating agent

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