Allergen-specific immunotherapy with Alutard SQ improves allergic inflammation in house-dust mites-induced allergic asthma rats through inactivation of the HMGB1/TLR4/NF-κB pathway

Journal of Thoracic Disease

article

Yingying Zhai¹  Peiyan Zheng³  Baoqing Sun³  Jing Li³  Bin Wang¹ 

[1] Department of Pediatrics, Zhujiang Hospital, Southern Medical University;Department of Pediatrics, The First Affiliated Hospital of Guangzhou Medical University;Department of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University

关键词: Asthma;    airway inflammation;    allergen-specific immunotherapy (AIT) with Alutard SQ;    HMGB1/TLR4/NF‐κB pathway;    house dust mite;   

DOI  :  10.21037/jtd-22-715

学科分类：呼吸医学

来源: Pioneer Bioscience Publishing Company

【 摘 要 】

Background: Allergen-specific immunotherapy (AIT) is the only available safe, effective, and long-term treatment for allergic airway diseases, including allergic asthma. However, the potential molecular mechanism of AIT in ameliorating airway inflammation remains unknown. Methods: Rats were sensitized and challenged with house dust mite (HDM) and administered with Alutard SQ or/and high mobility group box 1 (HMGB1) inhibitor, ammonium glycyrrhizinate (AMGZ) or HMGB1 lentivirus. The total and differential cell counts in rat bronchoalveolar lavage fluid (BALF) were detected. Hematoxylin and eosin staining (H&E) was performed to examine the pathological lesions in lung tissues. Enzyme-linked immunosorbent assay (ELISA) was performed to assess the expression of inflammatory factors in lungs, BALF, and serum. Quantitative real-time PCR (qRT-PCR) was used to measure the levels of inflammatory factors in the lungs. Western blot assay was used to evaluate the expression of HMGB1, Τoll-like receptor 4 (TLR4), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the lungs. Results: Consequently, AIT with Alutard SQ attenuated airway inflammation, the total and differential cells in BALF, and expression of Th (T helper)2 related cytokines and transforming growth factor beta 1 (TGF-β1). The regimen also upregulated Th-1-related cytokine expression by inhibiting the HMGB1/TLR4/NF-κB pathway in HDM-induced asthmatic rats. Furthermore, AMGZ, a HMGB1 antagonist, amplified the functions of AIT with Alutard SQ in the asthma rat model. Nevertheless, overexpression of HMGB1 reversed the functions of AIT with Alutard SQ in the asthma rat model. Conclusions: In summary, this work demonstrates the role of AIT with Alutard SQ, which inhibits the HMGB1/TLR4/NF-κB signaling pathway in allergic asthma management.

【 授权许可】

Unknown