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 journalArticlepeer-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 languageEnglish
Pages (from-to)646-652
Number of pages7
JournalBiochemical and biophysical research communications
Volume534
DOIs
Publication statusPublished - 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

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