Aim: The aim of this study was to examine if clusterin functions in regulating CCL20 production from BECs and is invovled with allergic airway inflammation through DC recruitment.
Methods: Clusterin knock-out (KO) mice were exposed to HDM extract for induction of allergic airway inflammation.The effect of clusterin on the production of CCL20 and various cytokines, development of allergic airway inflamation, immune cell recruitment into the lung, and intracellular reactive oxygen species (ROS) production was observed. CCL20 production and ROS generation was evaluated in HDM-stimulated human BECs in the setting of clusterin overexpression and downregulation.
Results: The number of total immune cells in bronchoalveolar lavage fluids (BALF) and lung were exhibited dramatic increases in clusterin KO mice. Inflammatory DCs (CD11b+CD11c+) and neutrophil populations in lung were also significantly increased, which was accompaied by enhanced CCL20 expression in BALF and oxidative stress marker expression in lung. In clusterin up- and down regulated BECs with HDM stimulation showed that secretion of CCL20 was negatively correlated with clusterin expression. Clusterin atteneuated intracellular ROS production which is related with induction of CCL20 expression after HDM stimulation.
Conclusion: Clusterin may modulate recruitment of DCs to the airway through regulating CCL20 production.