RT Journal Article
T1 Cannabinoid WIN55,212-2 restores bronchial epithelium by regulating oxidative stress and STAT6 phosphorylation
A1 Pérez Diego, Mario
A1 Angelina Querencias, Alba
A1 Pat, Yağız
A1 Maldonado, Angel
A1 Sevilla Ortega, Carmen
A1 Martín De La Cruz, Leticia
A1 Yazici, Duygu
A1 Rückert, Beate
A1 Sokolowska, Milena
A1 Martín-Fontecha Corrales, María Del Mar
A1 Akdis, Mübeccel
A1 Akdis, Cezmi A
A1 Palomares Gracia, Óscar
AB Background: Viral infections and type 2 immune responses perpetuate airway epithelial barrier dysfunction and inflammation, leading to the development and progression of asthma. The synthetic cannabinoid WIN55,212-2 displays anti-inflammatory properties by acting on different immune system cells.Objective: We sought to investigate the capacity of WIN55,212-2 to restore bronchial epithelial barrier function in asthma in the context of viral infections or type 2-driven inflammation.Methods: Air-liquid interface cultures of human bronchial epithelial cells and human bronchial epithelial spheroids were generated to assess the capacity of WIN55,212-2 to restore airway epithelial barrier damage induced by human rhinovirus A16 (RV-A16) infection or type 2 inflammation. RT-PCR, cytokine quantification, permeability assays, metabolic studies, flow cytometry, and Western blot techniques were employed to assess the effects of WIN55,212-2 on the airway epithelium. The in vivo relevance of our findings was evaluated in a murine model of IL-13-induced airway inflammation.Results: Prophylactic and therapeutic administration of WIN55,212-2 accelerated the recovery from RV-A16-induced bronchial epithelial barrier damage. WIN55,212-2 inhibited the acquisition of IL-13-induced type 2 asthma features in air-liquid interface cultures, self-assembled bronchial epithelial spheroids, and in vivo asthma model of airway inflammation and epithelial dysfunction. Mechanistically, WIN55,212-2 impaired IL-13-induced oxidative stress in epithelial cells, restoring the activity of protein tyrosine phosphatases, which in turn inhibited pSTAT6-mediated signaling pathways and asthma features.Conclusions: The cannabinoid WIN55,212-2 displays airway epithelial barrier protective effects during RV-A16 infection or type 2 inflammation by mechanisms associated with the modulation of oxidative metabolism and pSTAT6-mediated signaling.
PB PubMed
YR 2025
FD 2025-05
LK https://hdl.handle.net/20.500.14352/122508
UL https://hdl.handle.net/20.500.14352/122508
LA eng
NO Pérez-Diego M, Angelina A, Pat Y, Maldonado A, Sevilla-Ortega C, Martín-Cruz L, Yazici D, Rückert B, Sokolowska M, Martín-Fontecha M, Akdis M, Akdis CA, Palomares O. Cannabinoid WIN55,212-2 restores bronchial epithelium by regulating oxidative stress and STAT6 phosphorylation. J Allergy Clin Immunol. 2025 May 16:S0091-6749(25)00551-2. doi: 10.1016/j.jaci.2025.05.002. Epub ahead of print. PMID: 40383489.
NO Ministerio de Ciencia e Innovación (España)
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 22 mar 2026