IL-20 Cytokines Are Involved in Epithelial Lesions Associated with Virus-Induced COPD Exacerbation in Mice

Abstract

(1) Background: viral infections are a frequent cause of chronic obstructive pulmonary disease (COPD) exacerbations, which are responsible for disease progression and mortality. Previous reports showed that IL-20 cytokines facilitate bacterial lung infection, but their production and their role in COPD and viral infection has not yet been investigated. (2) Methods: C57BL/6 WT and IL-20 Rb KO mice were chronically exposed to air or cigarette smoke (CS) to mimic COPD. Cytokine production, antiviral response, inflammation and tissue damages were analyzed after PVM infection. (3) Results: CS exposure was associated with an increase in viral burden and antiviral response. PVM infection in CS mice enhanced IFN-γ, inflammation and tissue damage compared to Air mice. PVM infection and CS exposure induced, in an additive manner, IL-20 cytokines expression and the deletion of IL-20 Rb subunit decreased the expression of interferon-stimulated genes and the production of IFN-λ2/3, without an impact on PVM replication. Epithelial cell damages and inflammation were also reduced in IL-20 Rb-/- mice, and this was associated with reduced lung permeability and the maintenance of intercellular junctions. (4) Conclusions: PVM infection and CS exposure additively upregulates the IL-20 pathway, leading to the promotion of epithelial damages. Our data in our model of viral exacerbation of COPD identify IL-20 cytokine as a potential therapeutic target.

IL-20 Cytokines Are Involved in the Repair of Airway Epithelial Barrier: Implication in Exposure to Cigarette Smoke and in COPD Pathology

“…These results suggest that IL-20 cytokines that are produced in higher quantity in the context of CS exposure and/or by COPD patient airways could contribute to the defective repair capacity of the airway epithelium. Moreover, we recently demonstrated that IL-20 cytokines alter the epithelial barrier in the context of virus-induced exacerbation of COPD in mice by favoring the impact of the infection on the disorganization of intercellular junction protein [29]. This suggests that blocking IL-20 signaling could represent a potential therapeutic approach for COPD patients.…”

Cigarette smoke-induced gasdermin D activation in bronchoalveolar macrophages and bronchial epithelial cells dependently on NLRP3

“…The concentration of smoke particulates is estimated to be 350 mg/cubic meter as mentioned by the manufacturer as previously described ( 32 , 33 ). Our cigarette smoke exposure models are based on classical experimental models used to analyse the mechanism of CS-induced inflammation and/or COPD in mice ( 43 , 44 ). These smoke exposure models mimic important features observed in human including epithelial injury and pulmonary inflammation with neutrophils influx ( 1 , 2 , 6 ).…”