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Leukotriene enhanced allergic lung inflammation through induction of chemokine production

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Abstract

The leukotrienes (LTs) enhance allergen- and interleukin (IL)-13-dependent allergic lung inflammatory disease. However, the precise requirement of LTs and the mechanism by which they elicit allergic lung responses remain uncertain. To clarify the involvement of LTs in respiratory allergen- and IL-13-induced experimental asthma and elucidate the underlying mechanisms of LTs-mediated enhanced allergic asthma, we investigated the role of LTs in two models of allergic inflammation: intranasal Aspergillus protease allergen and recombinant IL-13-induced T helper type 2 (Th2) cell-mediated inflammation, and also examined Th2-related chemokines downstream of LTs signaling. 5-Lipoxygenase (5-LO)-deficient mice exposed to short-term intranasal Aspergillus protease allergen showed attenuated airway inflammation, decreased airway hyper-responsiveness and reduced bronchoalveolar eosinophilia when compared to wild-type mice. However, this phenotype was less apparent using long exposure to the same allergen. 5-LO-deficient mice exposed to intranasal rIL-13 also showed attenuated phenotypes of allergic asthma via significant reduction in Th2-specific chemokines, CCL7 and CCL17 production and decreased Th2 cells recruitment to the lungs. Addition of leukotriene B4 (LTB4) and LTC4 to the airways of 5-LO-deficient mice resulted in the rescue of rIL-13-induced experimental asthma. Furthermore, LTs addition to rIL-13 synergistically enhanced the production of Th2-specific chemokines in the lung and inflammatory responses. Therefore, our findings suggest that LTs complement allergens and their downstream cytokine (e.g., IL-13) induced Th2 inflammation by enhancing the induction of Th2 chemokines.

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Acknowledgments

We thank Jie Xu, Yu** Qian, Seang-Hwan Jung, Sang-Young Lee and Eun-Hye Choi for technical assistance, and all the members of the Hye Hwa Forum for helpful comments on the manuscript. This study was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MEST, 2012M3A9C7050093), a grant of the Korea Healthcare technology R&D Project, Ministry for Health, Welfare & Family Affairs, the Republic of Korea (A101284), the KAIST Future Systems Healthcare Project from the Ministry of Science, ICT and Future Planning, and Eulji University in 2008.

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Authors and Affiliations

  1. Cellular Immunology Laboratory, Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, Korea

    Kihyuk Shin, Jung Joo Hwang, Bo-In Kwon & Seung-Hyo Lee

  2. Department of Thoracic and Cardiovascular Surgery, Eulji University Hospital, Daejeon, 302-799, Korea

    Jung Joo Hwang

  3. Departments of Pathology and Immunology, and Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA

    Farrah Kheradmand & David B. Corry

  4. Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey VA, Houston, TX, 77030, USA

    Farrah Kheradmand & David B. Corry

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  1. Kihyuk Shin
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Correspondence to Seung-Hyo Lee.

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Kihyuk Shin and Jung Joo Hwang have made equal contributions to this work.

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Shin, K., Hwang, J.J., Kwon, BI. et al. Leukotriene enhanced allergic lung inflammation through induction of chemokine production. Clin Exp Med 15, 233–244 (2015). https://doi.org/10.1007/s10238-014-0292-7

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