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Article

Stress and Nasal Allergy: Corticotropin-Releasing Hormone Stimulates Mast Cell Degranulation and Proliferation in Human Nasal Mucosa

1
Department of Dermatology, Osaka City University Graduate School of Medicine, Osaka 5458585, Japan
2
Department of Otolaryngology and Head and Neck Surgery, Osaka City University Graduate School of Medicine, Osaka 5458585, Japan
3
Department of Research Support Platform, Osaka City University Graduate School of Medicine, Osaka 5458585, Japan
4
Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA
5
Centre for Dermatology Research, University of Manchester, and NIHR Manchester Biomedical Research Centre, Manchester M13 9PR, UK
6
Monasterium Laboratory, 48149 Münster, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Lars Hellman
Int. J. Mol. Sci. 2021, 22(5), 2773; https://doi.org/10.3390/ijms22052773
Received: 16 February 2021 / Revised: 27 February 2021 / Accepted: 6 March 2021 / Published: 9 March 2021
(This article belongs to the Section Molecular Biology)
Psychological stress exacerbates mast cell (MC)-dependent inflammation, including nasal allergy, but the underlying mechanisms are not thoroughly understood. Because the key stress-mediating neurohormone, corticotropin-releasing hormone (CRH), induces human skin MC degranulation, we hypothesized that CRH may be a key player in stress-aggravated nasal allergy. In the current study, we probed this hypothesis in human nasal mucosa MCs (hM-MCs) in situ using nasal polyp organ culture and tested whether CRH is required for murine M-MC activation by perceived stress in vivo. CRH stimulation significantly increased the number of hM-MCs, stimulated both their degranulation and proliferation ex vivo, and increased stem cell factor (SCF) expression in human nasal mucosa epithelium. CRH also sensitized hM-MCs to further CRH stimulation and promoted a pro-inflammatory hM-MC phenotype. The CRH-induced increase in hM-MCs was mitigated by co-administration of CRH receptor type 1 (CRH-R1)-specific antagonist antalarmin, CRH-R1 small interfering RNA (siRNA), or SCF-neutralizing antibody. In vivo, restraint stress significantly increased the number and degranulation of murine M-MCs compared with sham-stressed mice. This effect was mitigated by intranasal antalarmin. Our data suggest that CRH is a major activator of hM-MC in nasal mucosa, in part via promoting SCF production, and that CRH-R1 antagonists such as antalarmin are promising candidate therapeutics for nasal mucosa neuroinflammation induced by perceived stress. View Full-Text
Keywords: CRH; mast cell; nasal mucosa; psychological stress; stem cell factor (SCF) CRH; mast cell; nasal mucosa; psychological stress; stem cell factor (SCF)
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MDPI and ACS Style

Yamanaka-Takaichi, M.; Mizukami, Y.; Sugawara, K.; Sunami, K.; Teranishi, Y.; Kira, Y.; Paus, R.; Tsuruta, D. Stress and Nasal Allergy: Corticotropin-Releasing Hormone Stimulates Mast Cell Degranulation and Proliferation in Human Nasal Mucosa. Int. J. Mol. Sci. 2021, 22, 2773. https://doi.org/10.3390/ijms22052773

AMA Style

Yamanaka-Takaichi M, Mizukami Y, Sugawara K, Sunami K, Teranishi Y, Kira Y, Paus R, Tsuruta D. Stress and Nasal Allergy: Corticotropin-Releasing Hormone Stimulates Mast Cell Degranulation and Proliferation in Human Nasal Mucosa. International Journal of Molecular Sciences. 2021; 22(5):2773. https://doi.org/10.3390/ijms22052773

Chicago/Turabian Style

Yamanaka-Takaichi, Mika, Yukari Mizukami, Koji Sugawara, Kishiko Sunami, Yuichi Teranishi, Yukimi Kira, Ralf Paus, and Daisuke Tsuruta. 2021. "Stress and Nasal Allergy: Corticotropin-Releasing Hormone Stimulates Mast Cell Degranulation and Proliferation in Human Nasal Mucosa" International Journal of Molecular Sciences 22, no. 5: 2773. https://doi.org/10.3390/ijms22052773

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