Leukotriene B4 receptors play critical roles in house dust mites-induced neutrophilic airway inflammation and IL-17 production

Dong Wook Kwak; Donghwan Park; Jae Hong Kim

doi:10.1016/j.bbrc.2020.11.027

Leukotriene B₄ receptors play critical roles in house dust mites-induced neutrophilic airway inflammation and IL-17 production

Dong Wook Kwak, Donghwan Park, Jae Hong Kim

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

7 Citations (Scopus)

Abstract

Increased levels of neutrophils in bronchoalveolar lavage fluid (BALF) were associated with asthma severity. As leukotriene B4 (LTB₄) is a principal chemoattractant molecule for neutrophils, its receptors, BLT1 and BLT2, may contribute to neutrophil-dominant airway inflammation. In the present study, we established a mouse model of steroid-resistant, neutrophil-dominant airway inflammation by house dust mite (HDM)/lipopolysaccharide (LPS) sensitization and HDM challenge, and we investigated whether BLT1/BLT2 signaling was associated with the development of neutrophilic airway inflammation. Blockade of BLT1 or BLT2 significantly suppressed airway inflammation and IL-17 production in this mouse model. The 5-LO and 12-LO enzymes, which catalyze the synthesis of BLT1/BLT2 ligands, were also critically associated with neutrophil-dominant airway inflammation and the synthesis of IL-17. Collectively, our results suggest that the 5-/12-LO-BLT1/BLT2-linked cascade significantly contributes to neutrophil-dominant severe airway inflammation via IL-17 synthesis in HDM-induced neutrophilic asthma.

Original language	English
Pages (from-to)	646-652
Number of pages	7
Journal	Biochemical and biophysical research communications
Volume	534
DOIs	https://doi.org/10.1016/j.bbrc.2020.11.027
Publication status	Published - 2021 Jan 1

Bibliographical note

Funding Information:
This work was supported by Bio & Medical Technology Development Program grants ( 2017M3A9D8063317 ) and Mid-Career Researcher Program Grant ( 2020R1A2B5B01002046 ) through the National Research Foundation funded by the Ministry of Science, Information and Communication Technologies (ICT), and Future Planning , Republic of Korea. This work was also supported by the BK21 Plus Program (School of Life Sciences and Biotechnology, Korea University ).

Funding Information:
This work was supported by Bio & Medical Technology Development Program grants (2017M3A9D8063317) and Mid-Career Researcher Program Grant (2020R1A2B5B01002046) through the National Research Foundation funded by the Ministry of Science, Information and Communication Technologies (ICT), and Future Planning, Republic of Korea. This work was also supported by the BK21 Plus Program (School of Life Sciences and Biotechnology, Korea University).

Publisher Copyright:
© 2020 Elsevier Inc.

Keywords

Airway inflammation
HDM
IL-17
Leukotriene B4 receptors
Neutrophil

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

Access to Document

10.1016/j.bbrc.2020.11.027

Cite this

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title = "Leukotriene B4 receptors play critical roles in house dust mites-induced neutrophilic airway inflammation and IL-17 production",

abstract = "Increased levels of neutrophils in bronchoalveolar lavage fluid (BALF) were associated with asthma severity. As leukotriene B4 (LTB4) is a principal chemoattractant molecule for neutrophils, its receptors, BLT1 and BLT2, may contribute to neutrophil-dominant airway inflammation. In the present study, we established a mouse model of steroid-resistant, neutrophil-dominant airway inflammation by house dust mite (HDM)/lipopolysaccharide (LPS) sensitization and HDM challenge, and we investigated whether BLT1/BLT2 signaling was associated with the development of neutrophilic airway inflammation. Blockade of BLT1 or BLT2 significantly suppressed airway inflammation and IL-17 production in this mouse model. The 5-LO and 12-LO enzymes, which catalyze the synthesis of BLT1/BLT2 ligands, were also critically associated with neutrophil-dominant airway inflammation and the synthesis of IL-17. Collectively, our results suggest that the 5-/12-LO-BLT1/BLT2-linked cascade significantly contributes to neutrophil-dominant severe airway inflammation via IL-17 synthesis in HDM-induced neutrophilic asthma.",

keywords = "Airway inflammation, HDM, IL-17, Leukotriene B4 receptors, Neutrophil",

author = "Kwak, {Dong Wook} and Donghwan Park and Kim, {Jae Hong}",

note = "Funding Information: This work was supported by Bio & Medical Technology Development Program grants ( 2017M3A9D8063317 ) and Mid-Career Researcher Program Grant ( 2020R1A2B5B01002046 ) through the National Research Foundation funded by the Ministry of Science, Information and Communication Technologies (ICT), and Future Planning , Republic of Korea. This work was also supported by the BK21 Plus Program (School of Life Sciences and Biotechnology, Korea University ). Funding Information: This work was supported by Bio & Medical Technology Development Program grants (2017M3A9D8063317) and Mid-Career Researcher Program Grant (2020R1A2B5B01002046) through the National Research Foundation funded by the Ministry of Science, Information and Communication Technologies (ICT), and Future Planning, Republic of Korea. This work was also supported by the BK21 Plus Program (School of Life Sciences and Biotechnology, Korea University). Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

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N1 - Funding Information: This work was supported by Bio & Medical Technology Development Program grants ( 2017M3A9D8063317 ) and Mid-Career Researcher Program Grant ( 2020R1A2B5B01002046 ) through the National Research Foundation funded by the Ministry of Science, Information and Communication Technologies (ICT), and Future Planning , Republic of Korea. This work was also supported by the BK21 Plus Program (School of Life Sciences and Biotechnology, Korea University ). Funding Information: This work was supported by Bio & Medical Technology Development Program grants (2017M3A9D8063317) and Mid-Career Researcher Program Grant (2020R1A2B5B01002046) through the National Research Foundation funded by the Ministry of Science, Information and Communication Technologies (ICT), and Future Planning, Republic of Korea. This work was also supported by the BK21 Plus Program (School of Life Sciences and Biotechnology, Korea University). Publisher Copyright: © 2020 Elsevier Inc.

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N2 - Increased levels of neutrophils in bronchoalveolar lavage fluid (BALF) were associated with asthma severity. As leukotriene B4 (LTB4) is a principal chemoattractant molecule for neutrophils, its receptors, BLT1 and BLT2, may contribute to neutrophil-dominant airway inflammation. In the present study, we established a mouse model of steroid-resistant, neutrophil-dominant airway inflammation by house dust mite (HDM)/lipopolysaccharide (LPS) sensitization and HDM challenge, and we investigated whether BLT1/BLT2 signaling was associated with the development of neutrophilic airway inflammation. Blockade of BLT1 or BLT2 significantly suppressed airway inflammation and IL-17 production in this mouse model. The 5-LO and 12-LO enzymes, which catalyze the synthesis of BLT1/BLT2 ligands, were also critically associated with neutrophil-dominant airway inflammation and the synthesis of IL-17. Collectively, our results suggest that the 5-/12-LO-BLT1/BLT2-linked cascade significantly contributes to neutrophil-dominant severe airway inflammation via IL-17 synthesis in HDM-induced neutrophilic asthma.

AB - Increased levels of neutrophils in bronchoalveolar lavage fluid (BALF) were associated with asthma severity. As leukotriene B4 (LTB4) is a principal chemoattractant molecule for neutrophils, its receptors, BLT1 and BLT2, may contribute to neutrophil-dominant airway inflammation. In the present study, we established a mouse model of steroid-resistant, neutrophil-dominant airway inflammation by house dust mite (HDM)/lipopolysaccharide (LPS) sensitization and HDM challenge, and we investigated whether BLT1/BLT2 signaling was associated with the development of neutrophilic airway inflammation. Blockade of BLT1 or BLT2 significantly suppressed airway inflammation and IL-17 production in this mouse model. The 5-LO and 12-LO enzymes, which catalyze the synthesis of BLT1/BLT2 ligands, were also critically associated with neutrophil-dominant airway inflammation and the synthesis of IL-17. Collectively, our results suggest that the 5-/12-LO-BLT1/BLT2-linked cascade significantly contributes to neutrophil-dominant severe airway inflammation via IL-17 synthesis in HDM-induced neutrophilic asthma.

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