Anti-thymic stromal lymphopoietin antibody suppresses airway remodeling in asthma through reduction of MMP and CTGF

• Published in: Pediatric research 2019-08, Vol.86 (2), p.181-187
• Main Authors: Lin, Sheng-Chieh, Chou, Hsiu-Chu, Chen, Chung-Ming, Chiang, Bor-Luen
• Format: Article
• Language: English
• Subjects: Airway Remodeling; Animals; Antibodies, Monoclonal - pharmacology; Asthma; Asthma - metabolism; Basic Science Article; Connective Tissue Growth Factor - metabolism; Cytokines - immunology; Disease Models, Animal; Female; Growth factors; Immunoglobulin E - immunology; Inflammation; Lung - pathology; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinases - metabolism; Medicine; Medicine & Public Health; Methacholine Chloride; Mice; Mice, Inbred BALB C; Ovalbumin - blood; Ovalbumin - metabolism; Pediatric Surgery; Pediatrics; Plethysmography; Transforming Growth Factor beta - metabolism
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1038/s41390-018-0239-x

Background Thymic stromal lymphopoietin (TSLP) mediates immune reaction in patients with asthma. Matrix metalloproteinase (MMP), connective tissue growth factor (CTGF), and transforming growth factor-β (TGF-β) are inflammatory mediators whose responses to the anti-TSLP antibody are unknown. This study examined the effect of an anti-TSLP antibody on MMP, CTGF, TGF-β, and airway structural changes in airway remodeling in asthma. Methods Mice were randomly divided into phosphate-buffered-saline-challenged (PBS), ovalbumin-challenged (OVA), and ovalbumin-challenged with anti-TSLP antibody (OVA + anti-TSLP) groups. Airway responsiveness and serum ovalbumin-specific immunoglobulin E were measured. Differential cell counts and MMP-2 and MMP-9 were evaluated in bronchoalveolar lavage fluid (BALF). Airway structural changes were quantified using morphometric analysis and presentation by immunohistochemistry staining. Lung CTGF, TGF-β, and TSLP were analyzed using western blot. Results Airway responsiveness was significantly lower in OVA + anti-TSLP and PBS groups than in OVA group. Airway structural changes exhibited less smooth muscle thickness in OVA + anti-TSLP and PBS groups than in OVA group. MMP-2 and MMP-9 in BALF and CTGF, TGF-β, and TSLP in lungs significantly decreased in OVA + anti-TSLP and PBS groups compared with OVA group. Conclusion Anti-TSLP antibody exerts the preventive effect of decreasing airway structural changes through reduction of MMP, TGF-β, and CTGF in airway remodeling of asthma.