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Neuregulin-1 suppresses anti-apoptotic effect of Der p 38 on neutrophils by inhibition of cytokine secretion

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Abstract

Background

Neuregulin (NRG) plays essential roles in the growth and differentiation of epithelial, neuronal and glial cells. Asthma is a chronic respiratory disease characterized by airway constriction and caused by allergens such as Der p 38.

Objective

This study is aimed to investigate the relationship between NRG-1 and asthma-like inflammation due to allergens.

Results

Following Der p 38 intranasal or intraperitoneal/intranasal (IP/IN) administration in mice, the expression levels of NRG-1 and its receptors increased in response, including ErbB2 and ErbB4. We further examined the roles of NRG-1 in the human BEAS-2B lung epithelial cell line. Der p 38 enhanced NRG-1 expression in the cells and NRG-1 secretion was also upregulated in BEAS-2B cell supernatants treated with Der p 38. NRG-1 alone did not increase the release of interleukin-6 (IL-6), IL-8, or monocyte chemoattractant protein-1 (MCP-1), but it inhibited cytokine secretion increased by Der p 38. Direct treatment with NRG-1 did not affect alteration of neutrophil apoptosis due to Der p 38, but BEAS-2B cell supernatants treated with Der p 38 and NRG-1 blocked the antiapoptotic effects of Der p 38-treated supernatants on neutrophils by activation of caspase 9 and caspase 3.

Conclusion

NRG-1 may exhibit anti-inflammatory effects in a Der p 38-induced allergenic environment, particularly neutrophilic inflammation. The present study on NRG may open up approach opportunities for understanding of pathogenesis and treatment of asthma.

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Data availability

All datasets generated for this study are included in the manuscript.

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Acknowledgements

This work has been supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. NRF-2022R1F1A1075097).

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Author notes

  1. Yujin Hong and Ji Hyeon Choi have contributed equally to the work.

Authors and Affiliations

  1. Department of Senior Healthcare, Graduate School, Eulji University, Uijeongbu, 11759, Republic of Korea

    Yujin Hong, Min Hwa Hong, Geunyeong Kim & In Sik Kim

  2. Department of Biomedical Laboratory Science, College of Health Science, Eulji University, 712, Dongil-Ro, Uijeongbu, 11759, Republic of Korea

    Ji Hyeon Choi & In Sik Kim

  3. Department of Clinical Laboratory Science, Wonkwang Health Science University, Iksan, 54538, Republic of Korea

    Ji-Sook Lee

  4. Department of Anatomy and Neuroscience, Eulji University School of Medicine, Daejeon, 34824, Republic of Korea

    Ran-Sook Woo

  5. Department of Biomedical Laboratory Science, Daegu Haany University, 1, Hanuidae-Ro, Gyeongsan, 38610, Republic of Korea

    Eun Ju Yang

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  1. Yujin Hong
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Contributions

YH and JHC performed experiments, data collection, and data analysis. MHH, GK, JSL, and RSW, MSY analyzed the data and conducted statistical analysis. EJY, and ISK designed the study and wrote the manuscript.

Corresponding authors

Correspondence to Eun Ju Yang or In Sik Kim.

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Conflicts of interest

Yujin Hong, Ji Hyeon Choi, Min Hwa Hong, Geunyeong Kim, Ji-Sook Lee, Ran-Sook Woo, Eun Ju Yang, and In Sik Kim declare that they have no competing interests.

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All participants in this study gave their written informed consent.

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Hong, Y., Choi, J.H., Hong, M.H. et al. Neuregulin-1 suppresses anti-apoptotic effect of Der p 38 on neutrophils by inhibition of cytokine secretion. Mol. Cell. Toxicol. 19, 857–867 (2023). https://doi.org/10.1007/s13273-023-00375-w

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