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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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.
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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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DOI: https://doi.org/10.1007/s00408-024-00682-6