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

Int J Mol Sci. 2021 Mar 9;22(5):2773. doi: 10.3390/ijms22052773.


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.

Keywords: CRH; mast cell; nasal mucosa; psychological stress; stem cell factor (SCF).

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Degranulation / drug effects*
  • Cell Proliferation / drug effects*
  • Corticotropin-Releasing Hormone / pharmacology*
  • Female
  • Humans
  • Male
  • Mast Cells / metabolism*
  • Mast Cells / pathology
  • Middle Aged
  • Nasal Mucosa / metabolism*
  • Nasal Mucosa / pathology
  • Rhinitis, Allergic / metabolism*
  • Rhinitis, Allergic / pathology
  • Stress, Physiological / drug effects*


  • Corticotropin-Releasing Hormone