S Ben1, X Li, F Xu, W Xu, W Li, Z Wu, H Huang, H Shi, H Shen. 1. Department of Respiratory Disease, Second Affiliated Hospital, Zhejiang University College of Medicine, The Institute of Respiratory Diseases of Zhejiang University, Hangzhou, China.
Abstract
BACKGROUND: The migration and in situ differentiation of CD34(+) progenitors contribute to inflammatory eosinophilia in asthma and corticosteroids have been widely used in asthma. However, little is know about whether and how corticosteroids modulate the migration and differentiation of CD34(+) progenitors. This study was aimed to investigate the impact of anti-CC chemokine receptor 3 (CCR3) or dexamethasone on inflammatory eosinophilia in asthma and possible mechanism(s) underlying the action of dexamethasone or anti-CCR3 on migration and differentiation of CD34(+) progenitors in asthmatic context. METHODS: Using an asthmatic mouse model, airway inflammation of anti-CCR3- or dexamethasone-treated mice and that of controls were characterized. And the migration and differentiation of CD34(+) progenitor cells were analyzed in vivo, ex vivo or in vitro. RESULTS: Treatment with anti-CCR3 or dexamethasone significantly inhibited allergen-induced eosinophilia and CD34(+) progenitor cell infiltration in the lung, which was accompanied by lower levels of airway hyper-responsiveness and mucus production. Moreover, anti-CCR3 inhibited the eotaxin-mediated migration and IL-5/eotaxin-induced differentiation of CD34(+) progenitors in vitro. Dexamethasone was also shown to mitigate eotaxin-mediated migration and IL-5 or eotaxin-promoted differentiation of CD34(+) progenitor cells ex vivo, which were associated with the down-regulation of CCR3 expression on bone marrow progenitor cells. CONCLUSIONS: Treatment with anti-CCR3 or dexamethasone can inhibit the migration and differentiation of CD34(+) progenitor cells by regulating the eotaxin/CCR3 axis in asthmatic mice. Our findings provide new insights into understanding the mechanism(s) underlying the action of dexamethasone and CCR3-mediated signaling in allergic inflammation and aid in the design of new immunotherapy for intervention of human asthma.
BACKGROUND: The migration and in situ differentiation of CD34(+) progenitors contribute to inflammatory eosinophilia in asthma and corticosteroids have been widely used in asthma. However, little is know about whether and how corticosteroids modulate the migration and differentiation of CD34(+) progenitors. This study was aimed to investigate the impact of anti-CC chemokine receptor 3 (CCR3) or dexamethasone on inflammatory eosinophilia in asthma and possible mechanism(s) underlying the action of dexamethasone or anti-CCR3 on migration and differentiation of CD34(+) progenitors in asthmatic context. METHODS: Using an asthmatic mouse model, airway inflammation of anti-CCR3- or dexamethasone-treated mice and that of controls were characterized. And the migration and differentiation of CD34(+) progenitor cells were analyzed in vivo, ex vivo or in vitro. RESULTS: Treatment with anti-CCR3 or dexamethasone significantly inhibited allergen-induced eosinophilia and CD34(+) progenitor cell infiltration in the lung, which was accompanied by lower levels of airway hyper-responsiveness and mucus production. Moreover, anti-CCR3 inhibited the eotaxin-mediated migration and IL-5/eotaxin-induced differentiation of CD34(+) progenitors in vitro. Dexamethasone was also shown to mitigate eotaxin-mediated migration and IL-5 or eotaxin-promoted differentiation of CD34(+) progenitor cells ex vivo, which were associated with the down-regulation of CCR3 expression on bone marrow progenitor cells. CONCLUSIONS: Treatment with anti-CCR3 or dexamethasone can inhibit the migration and differentiation of CD34(+) progenitor cells by regulating the eotaxin/CCR3 axis in asthmatic mice. Our findings provide new insights into understanding the mechanism(s) underlying the action of dexamethasone and CCR3-mediated signaling in allergic inflammation and aid in the design of new immunotherapy for intervention of humanasthma.
Authors: Theodore S Johnson; Catherine E Terrell; Scott H Millen; Jonathan D Katz; David A Hildeman; Michael B Jordan Journal: J Immunol Date: 2013-11-20 Impact factor: 5.422
Authors: Alexander P P Lowe; Rhian S Thomas; Anthony T Nials; Emma J Kidd; Kenneth J Broadley; William R Ford Journal: J Pharmacol Exp Ther Date: 2017-06-02 Impact factor: 4.030