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KRN7000 Reduces Airway Inflammation via Natural Killer T Cells in Obese Asthmatic Mice

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Abstract

Although natural killer T cells (NKT cells) are altered in obese asthmatic mice, their function remains completely unclear. To further explore the potential mechanism of NKT cells in airway inflammation of obesity-associated asthma, we examined the effects of α-galactosylceramide (KRN7000) on airway inflammation in obese asthmatic mice. Male C57BL/6J mice were divided into five groups: (1) control; (2) asthma; (3) A + KRN, asthma with KRN7000; (4) obese asthma; and (5) OA + KRN, obese asthma with KRN7000. Cytometric bead array (CBA) was used to detect interleukin-4 (IL-4), IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in the serum. Flow cytometry was used to detect NKT cells and CD69+ NKT cells. Airway inflammation was observed in pathological sections, and calmodulin (CaM) expression was observed by immunohistochemistry in lung tissues. Airway inflammation in the obese asthma group was more severe than that of the asthma group. Airway inflammation of the OA + KRN group was reduced more than that of the A + KRN group. CD69+ NKT cells were only significantly reduced in the OA + KRN group. The levels of serum IFN-γ and TNF-α increased more in the OA + KRN group than in the A + KRN group. CaM is widely expressed in the cytoplasm of the lung tissues and was sharply decreased in the OA + KRN group. KRN7000 can significantly reduce airway inflammation in obesity-associated asthma by regulating NKT cell cytokine secretion and intracellular calcium. These results may contribute to the development of novel therapeutic approaches.

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Acknowledgments

The authors are grateful for the technical assistance of Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research.

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Funding

This research received funding from the Natural Science Foundation of Guangxi Province (Grant number: 2020JJA140130), the National Natural Science Foundation of China (Grant number: 81860005), Guangxi University Young and Middle-aged Teachers Basic Ability Improvement Project (Grant number:2017KY0106), Key Program “New Drug Creation” of Guangdong Key Research and Development Plan (Grant number: 2019B020202001)

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Author notes

  1. Yiping Chen, Yiping Zhu, Geng Su contributed equally to this work.

Authors and Affiliations

  1. The Affiliated Minzu Hospital of Guangxi Medical University/Guangxi Minzu Hospital, Nanning, Guangxi, 530001, People’s Republic of China

    Yiping Chen, Yiping Zhu, Geng Su, Yanying Zhao & Weiwei Lu

  2. Guangdong Lewwin Pharmaceutical Research Institute Co., Ltd, Guangzhou, Guangdong, 510990, People’s Republic of China

    Wei Yang

  3. The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530001, People’s Republic of China

    Jinghong Zhang

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  1. Yiping Chen
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In this work, Yiping Chen, and Jinghong Zhang designed study; Yiping Zhu, Geng Su, and Yanying Zhao performed research and analyzed data; Wei Yang contributed new methods or models; Yiping Chen and Weiwei Lu wrote the paper.

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Correspondence to Jinghong Zhang.

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All animal care and experimental protocols were approved by the Ethical Principles in Animal Research adopted by the Guangxi Medical University for Animal Experimentation, and followed the Guide for the Care and Use of Laboratory Animals.

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Chen, Y., Zhu, Y., Su, G. et al. KRN7000 Reduces Airway Inflammation via Natural Killer T Cells in Obese Asthmatic Mice. Inflammation 44, 1982–1992 (2021). https://doi.org/10.1007/s10753-021-01475-2

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