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IL-38 alleviates airway remodeling in chronic asthma via blocking the profibrotic effect of IL-36γ.
- Source :
- Clinical & Experimental Immunology; Dec2023, Vol. 214 Issue 3, p260-274, 15p
- Publication Year :
- 2023
-
Abstract
- Airway remodeling is a major feature of asthma. Interleukin (IL)-36γ is significantly upregulated and promotes airway hyper-responsiveness (AHR) in asthma, but its role in airway remodeling is unknown. Here, we aimed to investigate the role of IL-36γ in airway remodeling, and whether IL-38 can alleviate airway remodeling in chronic asthma by blocking the effects of IL-36γ. IL-36γ was quantified in mice inhaled with house dust mite (HDM). Extracellular matrix (ECM) deposition in lung tissues and AHR were assessed following IL-36γ administration to mice. Airway inflammation, AHR, and remodeling were evaluated after IL-38 or blocking IL-36 receptor (IL-36R) treatment in asthmatic mice. The effects of lung fibroblasts stimulated with IL-36γ and IL-38 were quantified in vitro. Increased expression of IL-36γ was detected in lung tissues of HDM-induced asthmatic mice. The intratracheal instillation of IL-36γ to mice significantly enhanced the ECM deposition, AHR, and the number of activated lung fibroblasts around the airways. IL-38 or blocking IL-36R treated asthmatic mice showed a significant alleviation in the airway inflammation, AHR, airway remodeling, and number of activated fibroblasts around airways as compared with the HDM group. In vitro, IL-36γ promoted the activation and migration of human lung fibroblasts (HFL-1). The administration of IL-38 can counteract these biological processes induced by IL-36γ in HFL-1cells. The results indicated that IL-38 can mitigate airway remodeling by blocking the profibrotic effects of IL-36γ in chronic asthma. IL-36γ may be a new therapeutic target, and IL-38 is a potential candidate agent for inhibiting airway remodeling in asthma. IL-36γ was upregulated in the lungs of chronic asthma mice, and it contributed to the airway remodeling. IL-38 can alleviate the airway remodeling in asthma by regulating the effect of IL-36γ. Graphical Abstract [ABSTRACT FROM AUTHOR]
- Subjects :
- HOUSE dust mites
ASTHMA
EXTRACELLULAR matrix
HUMAN migrations
Subjects
Details
- Language :
- English
- ISSN :
- 00099104
- Volume :
- 214
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Clinical & Experimental Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 174783794
- Full Text :
- https://doi.org/10.1093/cei/uxad099