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Updated: Jun 2, 2026
Murine Model of Allergen Induced Asthma
Published on: May 14, 2012
Targeting CD30L Alleviates Airway Remodeling via JNK/p38 MAPK Pathway in OVA-Induced Asthmatic Mice
Changjuan Xu1, Xiaofei Liu1, Rong Zeng1
1Department of Respiratory, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Respiratory Diseases, Featured Laboratory of Respiratory Immunology and Regenerative Medicine in Universities of Shandong, Jinan Clinical Research Center for Respiratory Disease, Jinan, China.
Purpose:
Airway remodeling is a key pathological feature of asthma. The CD30 ligand (CD30L), a member of the tumor necrosis factor (TNF) superfamily encoded by the Tnfsf8 gene, has been linked to immune-inflammatory pathologies. Nevertheless, the role of CD30L in airway remodeling has not been elucidated.
Methods:
We investigated CD30L expression and localization in lung specimens from asthma patients and ovalbumin (OVA)-induced asthmatic mice. Subsequently, we established asthmatic mice with macrophage-specific Tnfsf8 knockout or intranasal administration of recombinant CD30L protein, and analyzed airway pathology using multiple techniques. In vitro, an indirect co-culture system of macrophages and bronchial epithelial cells was employed to investigate the impact of CD30L on airway epithelial remodeling. The mechanisms of CD30L in human bronchial epithelial (HBE) cells were explored using small interfering RNA targeting CD30 (the receptor for CD30L), c-Jun N-terminal kinase (JNK) inhibitor, and p38 inhibitor.
Results:
CD30L expression was upregulated in asthmatic lung tissues (human/mice) and colocalized with macrophage markers. In vivo, macrophage-specific Tnfsf8 knockout attenuated extracellular matrix (ECM) deposition and epithelial-mesenchymal transition (EMT) during OVA-induced airway remodeling, whereas intranasal CD30L exacerbated these pathologies. Transcriptomic analysis of lung tissues revealed that CD30L regulated ECM deposition, cell adhesion, and epithelial cell migration. In vitro co-culture of macrophages with bronchial epithelial cells demonstrated that macrophage-specific CD30L silencing reversed remodeling-related proteins and EMT in bronchial epithelial cells. Furthermore, we found that CD30L significantly upregulated the JNK/p38 mitogen-activated protein kinase (MAPK) pathway in HBE cells. Silencing CD30 in HBE cells alleviated CD30L-induced remodeling and EMT, accompanied by downregulation of the JNK/p38 MAPK pathway. Treatment with JNK inhibitor (SP600125) or p38 inhibitor (SB203580) reversed the CD30L-induced pathological effects.
Conclusions:
Collectively, these findings demonstrate that CD30L critically regulates asthma airway remodeling via the JNK/p38 MAPK pathway, strongly suggesting its therapeutic potential as a target for airway remodeling in asthma.
