TY - JOUR
T1 - Role of interleukin 6 and its soluble receptor on the diffusion barrier dysfunction of alveolar tissue
AU - Sui, Chao
AU - Lee, Woo
N1 - Publisher Copyright: © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2023/12
Y1 - 2023/12
N2 - During respiratory infection, barrier dysfunction in alveolar tissue can result from “cytokine storm” caused by overly reactive immune response. Particularly, interleukin 6 (IL-6) is implicated as a key biomarker of cytokine storm responsible for and further progression to pulmonary edema. In this study, alveolar-like tissue was reconstructed in a microfluidic device with: (1) human microvascular lung endothelial cells (HULEC-5a) cultured under flow-induced shear stress and (2) human epithelial cells (Calu-3) cultured at air–liquid interface. The effects of IL-6 and the soluble form of its receptor (sIL-6R) on the permeability, electrical resistance, and morphology of the endothelial and epithelial layers were evaluated. The diffusion barrier properties of both the endothelial and epithelial layers were significantly degraded only when IL-6 treatment was combined with sIL-6R. As suggested by recent review and clinical studies, our results provide unequivocal evidence that the barrier dysfunction occurs through trans-signaling in which IL-6 and sIL-6R form a complex and then bind to the surface of endothelial and epithelial cells, but not by classical signaling in which IL-6 binds to membrane-expressed IL-6 receptor. This finding suggests that the role of both IL-6 and sIL-6R should be considered as important biomarkers in developing strategies for treating cytokine storm. Graphical Abstract: [Figure not available: see fulltext.]
AB - During respiratory infection, barrier dysfunction in alveolar tissue can result from “cytokine storm” caused by overly reactive immune response. Particularly, interleukin 6 (IL-6) is implicated as a key biomarker of cytokine storm responsible for and further progression to pulmonary edema. In this study, alveolar-like tissue was reconstructed in a microfluidic device with: (1) human microvascular lung endothelial cells (HULEC-5a) cultured under flow-induced shear stress and (2) human epithelial cells (Calu-3) cultured at air–liquid interface. The effects of IL-6 and the soluble form of its receptor (sIL-6R) on the permeability, electrical resistance, and morphology of the endothelial and epithelial layers were evaluated. The diffusion barrier properties of both the endothelial and epithelial layers were significantly degraded only when IL-6 treatment was combined with sIL-6R. As suggested by recent review and clinical studies, our results provide unequivocal evidence that the barrier dysfunction occurs through trans-signaling in which IL-6 and sIL-6R form a complex and then bind to the surface of endothelial and epithelial cells, but not by classical signaling in which IL-6 binds to membrane-expressed IL-6 receptor. This finding suggests that the role of both IL-6 and sIL-6R should be considered as important biomarkers in developing strategies for treating cytokine storm. Graphical Abstract: [Figure not available: see fulltext.]
KW - Cytokine Storm
KW - Endothelial barrier dysfunction
KW - Epithelial barrier dysfunction
KW - IL-6/sIL-6R
KW - Lung-on-chip model
KW - Respiratory infection
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U2 - 10.1007/s10544-023-00680-0
DO - 10.1007/s10544-023-00680-0
M3 - Article
C2 - 37851124
SN - 1387-2176
VL - 25
JO - Biomedical Microdevices
JF - Biomedical Microdevices
IS - 4
M1 - 40
ER -