Airway smooth muscle cells : regulators of airway inflammation

Airways from asthmatic subjects are more responsive to bronchoconstrictive stimuli than airways from healthy subjects. Airway smooth muscle (ASM) cells mediate contraction of the airways by responding to the bronchoconstrictive stimuli, which was thought to be the primary role of ASM cells. In this thesis, we have addressed the role of the secretory capacity of ASM cells in the regulation of airway inflammation in asthma. Using cultures, we have shown that ASM cells release various chemokines (eotaxin, eotaxin-3 and IL-8) involved in the recruitment of inflammatory cells in response to Th2 cytokines and the antimicrobial peptide LL-37. Also airway epithelial cells produce various chemokines in response to Th2 cytokines dependent on their status of differentiation. The IL-8 release by ASM cells is inhibited by the steroid budesonide whereas the combination of this steroid with the beta2-agonist formoterol (a combination often used by patients with asthma) did not further enhance the inhibitory effect. This suggests that other therapies should be developed to fully inhibit chemokine release by ASM cells. Our studies have helped to gain more insight into the role of ASM cells in airway inflammation in asthma and have led to further important research questions that remain to be addressed.LEI Universiteit LeidenPathogenese en behandeling van astm