Tulobuterol patch alleviates allergic asthmic inflammation by blockade of Syk and NF-κB activation in mice

// Lixia Fu 1, * , Jing Guan 2, * , Yujia Zhang 1, * , Pei Ma 1, * , Yuanyuan Zhuang 1 , Jinye Bai 1 , Yasi Ding 1 , Qi Hou 1 , Wan Gong 3 , Mingbao Lin 1 , Wensheng Zheng 1 and Jianmin Zhang 2 1 State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China 2 Beijing Shouer Pharmaceutical Factory, Capital Institute of Pediatrics, Beijing, China 3 College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China * These authors contributed equally to this work and are co-first authors Correspondence to: Mingbao Lin, email: mingbaolin@imm.cams.cn Wensheng Zheng, email: zhengwensheng@imm.ac.cn Jianmin Zhang, email: zjm051525@126.com Keywords: tulobuterol patch; allergic airway inflammation; mouse; Syk; NF-κB Received: September 25, 2017      Accepted: January 24, 2018      Published: January 31, 2018 ABSTRACT Background: Tulobuterol patch, one of strongest bronchodilators, was recently shown to improve bronchial hyperresponsiveness and significantly decrease the sputum eosinophil counts by combining with nonspecific anti-inflammatory drugs on patients with asthma. However, there is limited study on the anti-inflammatory activities of tulobuterol patch and its potential machenism. Results: The tulobuterol patch significantly ameliorated inflammatory cell infiltration in the lung tissue, reduced the number of total leukocytes and its differential count, markedly reduced the production of IL-1β, TNF-α, IL-6, CCL-11 and IL-4 in bronchial alveolar lavage fluid, as well as a reduction in IL-4/IFN-γ ratio. Tulobuterol patch exhibited the best effect on allergic inflammation compared with formoterol and salbutamol. Furthermore, tulobuterol patch treatment significantly suppressed the expression and activation of Syk and its downdream signaling NF-κB and p-NF-κB. Conclusions: The present studies revealed that tulobuterol patch effectively ameliorated airway inflammatory responses in allergic asthma, and its mechanisms, at least partially, via down-regulating Syk/NF-κB pathway. Methods: An ovalbumin induced allergic asthma mouse model were used, and the effects of tulobuterol patch on allergic airway inflammation were evaluated. Also, its anti-airway inflammatory potential was compared with two other β 2 -agonists, salbutamol and formoterol. Its possible anti-inflammatory mechanisms were identified by using western blotting and immunohistochemistry.