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Activated Leukocyte Cell Adhesion Molecule Regulates the Expression of Interleukin-33 in RSV Induced Airway Inflammation by Regulating MAPK Signaling Pathways

  • AIRWAY INFLAMMATION
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Abstract

Purpose

The respiratory syncytial virus (RSV) is a common respiratory virus that causes acute lower respiratory tract infectious diseases, particularly in young children and older individuals. Activated leukocyte cell adhesion molecule (ALCAM) is a membrane glycoprotein expressed in various cell types, including epithelial cells, and is associated with inflammatory responses and various cancers. However, the precise role of ALCAM in RSV-induced airway inflammation remains unclear, and our study aimed to explore this gap in the literature.

Methods

C57BL/6 wild-type, ALCAM knockout mice and airway epithelial cells were infected with RSV and the expression of ALCAM and inflammatory cytokines were measured. We also conducted further experiments using Anti-ALCAM antibody and recombinant ALCAM in airway epithelial cells.

Results

The expression levels of ALCAM and inflammatory cytokines increased in both RSV-infected mice and airway epithelial cells. Interestingly, IL-33 expression was significantly reduced in ALCAM-knockdown cells compared to control cells following RSV infection. Anti-ALCAM antibody treatment also reduced IL-33 expression following RSV infection. Furthermore, the phosphorylation of ERK1/2, p38, and JNK was diminished in ALCAM-knockdown cells compared to control cells following RSV infection. Notably, in the control cells, inhibition of these pathways significantly decreased the expression of IL-33. In vivo study also confirmed a reduction in inflammation induced by RSV infection in ALCAM deficient mice compared to wild-type mice.

Conclusion

These findings demonstrate that ALCAM contributes to RSV-induced airway inflammation at least partly by influencing IL-33 expression through mitogen-activated protein kinase signaling pathways. These results suggest that targeting ALCAM could be a potential therapeutic strategy for alleviating IL-33-associated lung diseases.

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Funding

This work was supported by a faculty research grant of Yonsei University College of Medicine (6-2019-0176) and the VITAL-Korea project from the Ministry of Health and Welfare (MoHW) of the Korean Government (Grant Number: HV22C0259) and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2018R1A5A2025079, 2021R1I1A1A01049002 and RS-2023-00208036).

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Author notes

  1. Seung Min Baek and Mi Na Kim have equally contributed to this work.

Authors and Affiliations

  1. Department of Pediatrics, Severance Hospital, Institute of Allergy, Institute for Immunology and Immunological Diseases, Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, South Korea

    Seung Min Baek, Mi Na Kim, Eun Gyul Kim, Yu Jin Lee, Chang Hyun Park, Min Jung Kim, Kyung Won Kim & Myung Hyun Sohn

  2. Department of Pediatrics, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin, South Korea

    Min Jung Kim

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  1. Seung Min Baek
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Contributions

SMB, MNK, and MHS contributed to the conception and design. SMB, MNK, EGK, YJL, CHP, and MJK contributed to experimental supports. SMB collected the data and wrote a first manuscript. SMB, MNK, EGK, KWK, and MHS contributed to analyze data and review the manuscript.

Corresponding authors

Correspondence to Min Jung Kim or Myung Hyun Sohn.

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Research Involving Animal Rights

All animal experiments were approved by the Institutional Animal Care and Use Committee of Yonsei University (Protocol No. 2023-0011; Seoul, Korea).

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Baek, S.M., Kim, M.N., Kim, E.G. et al. Activated Leukocyte Cell Adhesion Molecule Regulates the Expression of Interleukin-33 in RSV Induced Airway Inflammation by Regulating MAPK Signaling Pathways. Lung 202, 127–137 (2024). https://doi.org/10.1007/s00408-024-00682-6

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