House dust mite-induced Akt-ERK1/2-C/EBP beta pathway triggers CCL20-mediated inflammation and epithelial-mesenchymal transition for airway remodeling
- Authors
- Park, Shin-Young; Kang, Min-Jeong; Jin, Nuri; Lee, So Young; Lee, Yun Young; Jo, Sungsin; Eom, Jeong Yun; Han, Heejae; Chung, Sook In; Jang, Kiseok; Kim, Tae-Hwan; Park, Jungwon; Han, Joong-Soo
- Issue Date
- Sep-2022
- Publisher
- WILEY
- Keywords
- airway remodeling; asthma; CCL20 (C-C chemokine ligand 20); house dust mites; NLRP3 (Nod-like receptor family pyrin domain containing 3
- Citation
- FASEB JOURNAL, v.36, no.9, pp.1 - 19
- Indexed
- SCIE
SCOPUS
- Journal Title
- FASEB JOURNAL
- Volume
- 36
- Number
- 9
- Start Page
- 1
- End Page
- 19
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/171448
- DOI
- 10.1096/fj.202200150RR
- ISSN
- 0892-6638
- Abstract
- House dust mite (HDM) allergens cause inflammatory responses and chronic allergic diseases such as bronchial asthma and atopic dermatitis. Here, we investigate the mechanism by which HDM induces C-C chemokine ligand 20 (CCL20) expression to promote chronic inflammation and airway remodeling in an HDM-induced bronchial asthma mouse model. We showed that HDM increased CCL20 levels via the Akt-ERK1/2-C/EBP beta pathway. To investigate the role of CCL20 in chronic airway inflammation and remodeling, we made a mouse model of CCL20-induced bronchial asthma. Treatment of anti-CCL20Ab in this mouse model showed the reduced airway hyper-responsiveness and inflammatory cell infiltration into peribronchial region by neutralizing CCL20. In addition, CCL20 induced the Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation through NLRP3 deubiquitination and transcriptional upregulation in BEAS-2B cells. As expected, anti-CCL20Ab markedly suppressed NLRP3 activation induced by CCL20. Moreover, HDM-induced CCL20 leads to epithelial-mesenchymal transition in the lung epithelium which appears to be an important regulator of airway remodeling in allergic asthma. We also found that anti-CCL20Ab attenuates airway inflammation and remodeling in an HDM-induced mouse model of bronchial asthma. Taken together, our results suggest that HDM-induced CCL20 is required for chronic inflammation that contributes airway remodeling in a mouse model of asthma.
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