Inhibition of high-mobility group box 1 in lung reduced airway inflammation and remodeling in a mouse model of chronic asthma |
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| Authors: | Chen-Chen Lee Yu-Ting Lai Hao-Teng Chang Jiunn-Wang Liao Woei-Cherng Shyu Chi-Yuan Li Chien-Neng Wang |
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| Institution: | 1. Department of Microbiology and Immunology, School of Medicine, China Medicine University, Taichung, Taiwan;2. Graduate Institute of Immunology, College of Medicine, China Medicine University, Taichung, Taiwan;3. Graduate Institute of Molecular System Biomedicine, College of Medicine, China Medicine University, Taichung, Taiwan;4. Graduate Institute of Veterinary Pathology, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan;5. Graduate Institute of Clinical Medical Science, College of Medicine, China Medicine University, Taichung, Taiwan;6. Graduate Institute of Basic Medical Science, College of Medicine, China Medicine University, Taichung, Taiwan |
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| Abstract: | The role of high-mobility group box 1 (HMGB1) in chronic allergic asthma is currently unclear. Both airway neutrophilia and eosinophilia and increase in HMGB1 expression in the lungs in our murine model of chronic asthma. Inhibition of HMGB1 expression in lung in ovalbumin (OVA)-immunized mice decreased induced airway inflammation, mucus formation, and collagen deposition in lung tissues. Analysis of the numbers of CD4+ T helper (Th) cells in the mediastinal lymph nodes and lungs revealed that Th17 showed greater increases than Th2 cells and Th1 cells in OVA-immunized mice; further, the numbers of Th1, Th2, and Th17 cells decreased in anti-HMGB1 antibody (Ab)-treated mice. In OVA-immunized mice, TLR-2 and TLR-4 expression, but not RAGE expression, was activated in the lungs and attenuated after anti-HMGB1 Ab treatment. The results showed that increase in HMGB1 release and expression in the lungs could be an important pathological mechanism underlying chronic allergic asthma and HMGB1 might a potential therapeutic target for chronic allergic asthma. |
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| Keywords: | HMGB1 Airway inflammation Airway remodeling IL-17 |
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