Stress and nasal allergy: Corticotropin-releasing hormone stimulates mast cell degranulation and proliferation in human nasal mucosa

Mika Yamanaka-Takaichi, Yukari Mizukami, Koji Sugawara, Kishiko Sunami, Yuichi Teranishi, Yukimi Kira, Ralf Paus, Daisuke Tsuruta

Research output: Contribution to journalArticlepeer-review

Abstract

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 an-talarmin, 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 neu-roinflammation induced by perceived stress.

Original languageEnglish (US)
Article number2773
Pages (from-to)1-20
Number of pages20
JournalInternational journal of molecular sciences
Volume22
Issue number5
DOIs
StatePublished - Mar 1 2021

Keywords

  • CRH
  • Mast cell
  • Nasal mucosa
  • Psychological stress
  • Stem cell factor (SCF)

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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