IL-37 protects against house dust mite-induced airway inflammation and airway epithelial barrier dysfunction via inhibiting store-operated calcium entry

Int Immunopharmacol. 2024 Sep 10:138:112525. doi: 10.1016/j.intimp.2024.112525. Epub 2024 Jun 27.

Abstract

Background: Airway epithelial barrier dysfunction has been proved to contribute to the development of type 2 inflammation of asthma. Interleukin (IL)-37 is a negative regulator of immune responses and allergic airway inflammation. However, whether IL-37 has any effect on airway epithelial barrier has been unknown.

Methods: We evaluated the role of IL-37 in both mouse model and cultured 16HBE cells. Histology and ELISA assays were used to evaluate airway inflammation. FITC-dextran permeability assay was used to evaluate the airway epithelial barrier function. Immunofluorescence, western blot and quantitative Real-Time PCR (RT-PCR) were used to evaluate the distribution and expression of tight junction proteins. RT-PCR and Ca2+ fluorescence measurement were used to evaluate the mRNA expression and activity of store-operated calcium entry (SOCE).

Results: IL-37 inhibited house dust mite (HDM)-induced airway inflammation and decreased the levels of IgE in serum and type 2 cytokines in bronchoalveolar lavage fluid (BALF) compared to asthmatic mice. IL-37 protected against HDM-induced airway epithelial barrier dysfunction, including reduced leakage of FITC-dextran, enhanced expression of TJ proteins, and restored the membrane distribution of TJ proteins. Moreover, IL-37 decreased the level of IL-33 in the BALF of asthmatic mice and the supernatants of HDM-treated 16HBE cells. IL-37 decreased the peak level of Ca2+ fluorescence induced by thapsigargin and HDM, and inhibited the mRNA expression of Orai1, suggesting an inhibiting effect of IL-37 on SOCE in airway epithelial cells.

Conclusion: IL-37 plays a protective role in airway inflammation and HDM-induced airway epithelial barrier dysfunction by inhibiting SOCE.

Keywords: Airway epithelial barrier; Allergic asthma; House dust mite; Interleukin-37; Store-operated calcium entry.

MeSH terms

  • Animals
  • Asthma* / immunology
  • Asthma* / metabolism
  • Bronchoalveolar Lavage Fluid / immunology
  • Calcium* / metabolism
  • Cell Line
  • Cytokines / metabolism
  • Disease Models, Animal
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Female
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Interleukin-1* / metabolism
  • Mice
  • ORAI1 Protein / genetics
  • ORAI1 Protein / metabolism
  • Pyroglyphidae* / immunology
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism

Substances

  • Calcium
  • Cytokines
  • Immunoglobulin E
  • Interleukin-1
  • ORAI1 Protein