Page 18 - H. Cell signaling

[H. Cell signaling-16]

HDM-induced Chemokine CCL20 regulates Chronic

Inflammation and Remodeling of Airway in Mouse Model of

Bronchial Asthma

Shin-Young Park¹, Min-Jeong Kang¹, Yunyoung Lee², Soyoung Lee¹, Heejae Han³, Jungwon Park³, Joong-Soo Han¹

¹Biochemistry & Molecular Biology, Hanyang University, Seoul 04763, Republic of Korea, ²Research, Gencurix,

Seoul 08394, Republic of Korea, ³Allergy and Immunology, Yonsei University, Seoul 03722, Republic of Korea

In this study, we investigated the mechanism by which HDM induces C-C chemokine ligand 20 (CCL20) expressions
to promote chronic inflammation and remodeling of airway in mouse model of bronchial asthma. We showed that

HDM increased CCL20 expression, and its expression was regulated by PI3K/Akt/ERK1/2 pathway. To investigated
the role of CCL20 in chronic inflammation and remodeling of the airway, we performed studies using a mouse

model of CCL20-induced bronchial asthma. CCL20 inhibition using neutralizing anti-CCL20 antibody reduced airway
hyper-responsiveness and the infiltration of inflammatory cells. It also inhibited mucus-containing goblet cells

around the bronchial airway and collagen deposition around the bronchi. Furthermore, anti-CCL20 neutralizing
suppressed the activation of NLRP3 inflammasome, including the secretion of IL-1β which contributes to enhance

lung fibrosis in asthma. In addition, IL-1β increased the expression of the fibrotic genes, α-SMA and TGF-β1, so
appears to be an important regulator for lung fibrosis. Taken together, these results suggest that HDM-induced

chemokine CCL20 is required for chronic inflammation and has a profibrotic effect in the remodeling of airway in
mouse model of bronchial asthma.