Leukotriene B4 Receptor 2 Mediates the Production of G-CSF That Plays a Critical Role in Steroid-Resistant Neutrophilic Airway Inflammation

Dong Wook Kwak, Donghwan Park, Jae Hong Kim

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    5 Citations (Scopus)

    Abstract

    Granulocyte colony-stimulating factor (G-CSF) has been suggested to be closely associated with neutrophilic asthma pathogenesis. However, little is known about the factors regulating the production of G-CSF in neutrophilic asthma. We previously reported that a leukotriene B4 receptor 2, BLT2, played an important role in neutrophilic airway inflammation. Therefore, in the current study, we investigated whether BLT2 plays a role in the production of G-CSF in lipopolysaccharide/ovalbumin (LPS/OVA)-induced steroid-resistant neutrophilic asthma. The data showed that BLT2 critically mediated G-CSF production, contributing to the progression of neutrophilic airway inflammation. We also observed that 12-lipoxygenase (12-LO), which catalyzes the synthesis of the BLT2 ligand 12(S)-HETE, was also necessary for G-CSF production. Together, these results suggest that the 12-LO-BLT2-linked signaling network is critical for the production of G-CSF, contributing to the development of neutrophilic airway inflammation. Our findings can provide a potential new target for the therapy of severe neutrophilic asthma.

    Original languageEnglish
    Article number2979
    JournalBiomedicines
    Volume10
    Issue number11
    DOIs
    Publication statusPublished - 2022 Nov

    Bibliographical note

    Funding Information:
    This work was supported by a Bio and Medical Technology Development Program grant (2017M3A9D8063317) through the National Research Foundation (NRF) funded by the Ministry of Science, Information and Communication Technologies (ICT) and Future Planning of the Republic of Korea. This work was also supported by a Korea University Grant.

    Publisher Copyright:
    © 2022 by the authors.

    Keywords

    • 12-LO
    • airway inflammation
    • BLT2
    • G-CSF
    • neutrophil

    ASJC Scopus subject areas

    • Medicine (miscellaneous)
    • General Biochemistry,Genetics and Molecular Biology

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