Therapeutic effects of SKF-96365 on murine allergic rhinitis induced by OVA

Int J Immunopathol Pharmacol. 2021 Jan-Dec:35:20587384211015054. doi: 10.1177/20587384211015054.

Abstract

Introduction: SKF-96365 is regarded as an inhibitor of receptor-mediated calcium ion (Ca2+) entry. The current study aimed to explore the effects of SKF-96365 on murine allergic rhinitis (AR).

Methods: Intranasal SKF-96365 administration was performed on OVA induced murine AR. Serum and nasal lavage fluid (NLF) from mice were harvested to assay IgE and inflammatory cytokines using ELISA method. Inflammatory cells were counted and analyzed in NLF. Nasal mucosa tissues were collected from mice and used for HE staining, immunohistochemistry (IHC) staining, and real-time PCR detection.

Results: SKF-96365 had therapeutic effects on murine AR manifesting attenuation of sneezing, nasal rubbing, IgE, inflammatory cytokines, inflammatory cells, TRPC6 immunolabeling, and TRPC6, STIM1 and Orai1 mRNA levels in AR mice.

Conclusion: SKF-96365 could effectively alleviate the symptoms of murine AR. SKF-96365 could suppress TRPC6, STIM1, and Orai1 activities, leading to the downregulation of inflammatory cytokines and inflammatory cells in murine AR.

Keywords: Orai1; SKF-96365; STIM1; TRPC6; allergic rhinitis; calcium; ovalbumin.

MeSH terms

  • Allergens
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Cytokines / blood
  • Cytokines / immunology
  • Disease Models, Animal
  • Eosinophils / drug effects
  • Eosinophils / immunology
  • Female
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use*
  • Mice
  • Mice, Inbred BALB C
  • Nasal Lavage Fluid / cytology
  • Nasal Lavage Fluid / immunology
  • Nasal Mucosa / drug effects
  • Nasal Mucosa / immunology
  • ORAI1 Protein / genetics
  • Ovalbumin
  • Rhinitis, Allergic / blood
  • Rhinitis, Allergic / drug therapy*
  • Rhinitis, Allergic / genetics
  • Rhinitis, Allergic / immunology
  • Stromal Interaction Molecule 1 / genetics
  • TRPC6 Cation Channel / genetics
  • TRPC6 Cation Channel / immunology

Substances

  • Allergens
  • Anti-Inflammatory Agents
  • Cytokines
  • Imidazoles
  • ORAI1 Protein
  • Orai1 protein, mouse
  • Stim1 protein, mouse
  • Stromal Interaction Molecule 1
  • TRPC6 Cation Channel
  • Trpc6 protein, mouse
  • Ovalbumin
  • 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole