House dust mite-induced Akt-ERK1/2-C/EBP beta pathway triggers CCL20-mediated inflammation and epithelial–mesenchymal transition for airway remodeling

Shin Young Park; Min Jeong Kang; Nuri Jin; So Young Lee; Yun Young Lee; Sungsin Jo; Jeong Yun Eom; Heejae Han; Sook In Chung; Kiseok Jang; Tae Hwan Kim; Jungwon Park; Joong Soo Han

doi:10.1096/fj.202200150RR

House dust mite-induced Akt-ERK1/2-C/EBP beta pathway triggers CCL20-mediated inflammation and epithelial–mesenchymal transition for airway remodeling

Shin Young Park, Min Jeong Kang, Nuri Jin, So Young Lee, Yun Young Lee, Sungsin Jo, Jeong Yun Eom, Heejae Han, Sook In Chung, Kiseok Jang, Tae Hwan Kim, Jungwon Park, Joong Soo Han

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

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/EBPβ 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.

Original language	English
Article number	e22452
Journal	FASEB Journal
Volume	36
Issue number	9
DOIs	https://doi.org/10.1096/fj.202200150RR
Publication status	Published - 2022 Sept

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2021R1A2C1008317), and partly supported by the National Research Foundation of Korea (NRF), which is funded by the Ministry of Science, ICT, and Future Planning (2018R1A1A1A05022185). We also thank Prof. Eung-Gook Kim (Chungbuk University, Republic of Korea) for providing IMR90 cells in this study.

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2021R1A2C1008317), and partly supported by the National Research Foundation of Korea (NRF), which is funded by the Ministry of Science, ICT, and Future Planning (2018R1A1A1A05022185). We also thank Prof. Eung‐Gook Kim (Chungbuk University, Republic of Korea) for providing IMR90 cells in this study.

Publisher Copyright:
© 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.

All Science Journal Classification (ASJC) codes

Biotechnology
Biochemistry
Molecular Biology
Genetics

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10.1096/fj.202200150RR

Cite this

Park, S. Y., Kang, M. J., Jin, N., Lee, S. Y., Lee, Y. Y., Jo, S., Eom, J. Y., Han, H., Chung, S. I., Jang, K., Kim, T. H., Park, J., & Han, J. S. (2022). House dust mite-induced Akt-ERK1/2-C/EBP beta pathway triggers CCL20-mediated inflammation and epithelial–mesenchymal transition for airway remodeling. FASEB Journal, 36(9), [e22452]. https://doi.org/10.1096/fj.202200150RR

@article{4812e771a25e4b5ba0438cf0308eb424,

title = "House dust mite-induced Akt-ERK1/2-C/EBP beta pathway triggers CCL20-mediated inflammation and epithelial–mesenchymal transition for airway remodeling",

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/EBPβ 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.",

author = "Park, {Shin Young} and Kang, {Min Jeong} and Nuri Jin and Lee, {So Young} and Lee, {Yun Young} and Sungsin Jo and Eom, {Jeong Yun} and Heejae Han and Chung, {Sook In} and Kiseok Jang and Kim, {Tae Hwan} and Jungwon Park and Han, {Joong Soo}",

note = "Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2021R1A2C1008317), and partly supported by the National Research Foundation of Korea (NRF), which is funded by the Ministry of Science, ICT, and Future Planning (2018R1A1A1A05022185). We also thank Prof. Eung-Gook Kim (Chungbuk University, Republic of Korea) for providing IMR90 cells in this study. Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2021R1A2C1008317), and partly supported by the National Research Foundation of Korea (NRF), which is funded by the Ministry of Science, ICT, and Future Planning (2018R1A1A1A05022185). We also thank Prof. Eung‐Gook Kim (Chungbuk University, Republic of Korea) for providing IMR90 cells in this study. Publisher Copyright: {\textcopyright} 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.",

year = "2022",

month = sep,

doi = "10.1096/fj.202200150RR",

language = "English",

volume = "36",

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T1 - House dust mite-induced Akt-ERK1/2-C/EBP beta pathway triggers CCL20-mediated inflammation and epithelial–mesenchymal transition for airway remodeling

AU - Park, Shin Young

AU - Kang, Min Jeong

AU - Jin, Nuri

AU - Lee, So Young

AU - Lee, Yun Young

AU - Jo, Sungsin

AU - Eom, Jeong Yun

AU - Han, Heejae

AU - Chung, Sook In

AU - Jang, Kiseok

AU - Kim, Tae Hwan

AU - Park, Jungwon

AU - Han, Joong Soo

N1 - Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2021R1A2C1008317), and partly supported by the National Research Foundation of Korea (NRF), which is funded by the Ministry of Science, ICT, and Future Planning (2018R1A1A1A05022185). We also thank Prof. Eung-Gook Kim (Chungbuk University, Republic of Korea) for providing IMR90 cells in this study. Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2021R1A2C1008317), and partly supported by the National Research Foundation of Korea (NRF), which is funded by the Ministry of Science, ICT, and Future Planning (2018R1A1A1A05022185). We also thank Prof. Eung‐Gook Kim (Chungbuk University, Republic of Korea) for providing IMR90 cells in this study. Publisher Copyright: © 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.

PY - 2022/9

Y1 - 2022/9

N2 - 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/EBPβ 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.

AB - 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/EBPβ 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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ER -

House dust mite-induced Akt-ERK1/2-C/EBP beta pathway triggers CCL20-mediated inflammation and epithelial–mesenchymal transition for airway remodeling

Abstract

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