Tranexamic acid blocks the thrombin-mediated delay of epidermal permeability barrier recovery induced by the cedar pollen allergen, Cry j1

Abstract We previously demonstrated that Cry j1, the major pollen allergen of Cryptomeria japonica (Japanese cedar), transiently increases protease activity and intracellular Ca2+ concentration in cultured human keratinocytes, and delays recovery after stratum corneum barrier disruption in human ski...

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Autores principales:	S. Nakanishi, J. Kumamoto, M. Denda
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Barrier Recovery Tranexamic Acid Epidermal Permeability Barrier Cedar Pollen Allergen Bivalirudin Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4fbe40c17c1e4fac9be321db7ed0227e
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spelling	oai:doaj.org-article:4fbe40c17c1e4fac9be321db7ed0227e2021-12-02T15:09:12ZTranexamic acid blocks the thrombin-mediated delay of epidermal permeability barrier recovery induced by the cedar pollen allergen, Cry j110.1038/s41598-018-33898-72045-2322https://doaj.org/article/4fbe40c17c1e4fac9be321db7ed0227e2018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33898-7https://doaj.org/toc/2045-2322Abstract We previously demonstrated that Cry j1, the major pollen allergen of Cryptomeria japonica (Japanese cedar), transiently increases protease activity and intracellular Ca2+ concentration in cultured human keratinocytes, and delays recovery after stratum corneum barrier disruption in human skin ex vivo. Topical application of tranexamic acid or trypsin-type serine protease inhibitors accelerates barrier recovery. We hypothesized that tranexamic acid might prevent the transient protease activity increase and the barrier recovery delay induced by Cry j1. Here, we tested this hypothesis and examined the mechanism involved. In cultured human keratinocytes, knock-down of protease-activated receptor 1 (PAR-1) reduced the transient increase of calcium induced by Cry j1, whereas knock-down of PAR-2 did not. Knock-down of thrombin significantly reduced the transient increases of calcium concentration and protease activity. Tranexamic acid, soybean trypsin inhibitor, or bivalirudin (a thrombin inhibitor) also reduced the calcium elevation induced by Cry j1 and/or thrombin. Co-application of tranexamic acid or bivalirudin with Cry j1 to human skin ex vivo blocked the delay of barrier recovery. These results suggest that thrombin and PAR-1 or PAR-1-like receptor might mediate the adverse effects of Cry j1 on human epidermal keratinocytes, and could open up a new strategy for treating inflammatory skin diseases.S. NakanishiJ. KumamotoM. DendaNature PortfolioarticleBarrier RecoveryTranexamic AcidEpidermal Permeability BarrierCedar Pollen AllergenBivalirudinMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Barrier Recovery Tranexamic Acid Epidermal Permeability Barrier Cedar Pollen Allergen Bivalirudin Medicine R Science Q
spellingShingle	Barrier Recovery Tranexamic Acid Epidermal Permeability Barrier Cedar Pollen Allergen Bivalirudin Medicine R Science Q S. Nakanishi J. Kumamoto M. Denda Tranexamic acid blocks the thrombin-mediated delay of epidermal permeability barrier recovery induced by the cedar pollen allergen, Cry j1
description	Abstract We previously demonstrated that Cry j1, the major pollen allergen of Cryptomeria japonica (Japanese cedar), transiently increases protease activity and intracellular Ca2+ concentration in cultured human keratinocytes, and delays recovery after stratum corneum barrier disruption in human skin ex vivo. Topical application of tranexamic acid or trypsin-type serine protease inhibitors accelerates barrier recovery. We hypothesized that tranexamic acid might prevent the transient protease activity increase and the barrier recovery delay induced by Cry j1. Here, we tested this hypothesis and examined the mechanism involved. In cultured human keratinocytes, knock-down of protease-activated receptor 1 (PAR-1) reduced the transient increase of calcium induced by Cry j1, whereas knock-down of PAR-2 did not. Knock-down of thrombin significantly reduced the transient increases of calcium concentration and protease activity. Tranexamic acid, soybean trypsin inhibitor, or bivalirudin (a thrombin inhibitor) also reduced the calcium elevation induced by Cry j1 and/or thrombin. Co-application of tranexamic acid or bivalirudin with Cry j1 to human skin ex vivo blocked the delay of barrier recovery. These results suggest that thrombin and PAR-1 or PAR-1-like receptor might mediate the adverse effects of Cry j1 on human epidermal keratinocytes, and could open up a new strategy for treating inflammatory skin diseases.
format	article
author	S. Nakanishi J. Kumamoto M. Denda
author_facet	S. Nakanishi J. Kumamoto M. Denda
author_sort	S. Nakanishi
title	Tranexamic acid blocks the thrombin-mediated delay of epidermal permeability barrier recovery induced by the cedar pollen allergen, Cry j1
title_short	Tranexamic acid blocks the thrombin-mediated delay of epidermal permeability barrier recovery induced by the cedar pollen allergen, Cry j1
title_full	Tranexamic acid blocks the thrombin-mediated delay of epidermal permeability barrier recovery induced by the cedar pollen allergen, Cry j1
title_fullStr	Tranexamic acid blocks the thrombin-mediated delay of epidermal permeability barrier recovery induced by the cedar pollen allergen, Cry j1
title_full_unstemmed	Tranexamic acid blocks the thrombin-mediated delay of epidermal permeability barrier recovery induced by the cedar pollen allergen, Cry j1
title_sort	tranexamic acid blocks the thrombin-mediated delay of epidermal permeability barrier recovery induced by the cedar pollen allergen, cry j1
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/4fbe40c17c1e4fac9be321db7ed0227e
work_keys_str_mv	AT snakanishi tranexamicacidblocksthethrombinmediateddelayofepidermalpermeabilitybarrierrecoveryinducedbythecedarpollenallergencryj1 AT jkumamoto tranexamicacidblocksthethrombinmediateddelayofepidermalpermeabilitybarrierrecoveryinducedbythecedarpollenallergencryj1 AT mdenda tranexamicacidblocksthethrombinmediateddelayofepidermalpermeabilitybarrierrecoveryinducedbythecedarpollenallergencryj1
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Tranexamic acid blocks the thrombin-mediated delay of epidermal permeability barrier recovery induced by the cedar pollen allergen, Cry j1

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