Cilomilast Modulates Rhinovirus-Induced Airway Epithelial ICAM-1 Expression and IL-6, CXCL8 and CCL5 Production

Background: Cilomilast, a phosphodiesterase-4 (PDE4) selective inhibitor, has anti-inflammatory effects in vitro and in vivo and reduces COPD exacerbations. We tested the hypothesis that cilomilast inhibits virus-induced airway epithelial intercellular adhesion molecule-1 (ICAM-1) expression and inflammatory cytokine/chemoattractants, IL-6, CXCL8, and CCL5 production in vitro. Methods: BEAS-2B bronchial epithelial cells were incubated with 0.5-2 MOI (multiplicity of infection-infectious units/cell) of rhinovirus 16 (RV16). Then, 0.1-10 μM cilomilast or 10 nM dexamethasone, as inhibition control, were added pre- or post-1 h RV16 infection. Supernatant and cells were sampled at 8, 24, 48, and 72 h after infection. Cell surface ICAM-1 expression was detected by immunogold labelling and visualised by high-resolution scanning electron microscopy (HR-SEM), while IL-6, CXCL8, and CCL5 protein release and mRNA expression were measured using an ELISA and RT-PCR. Results: Cilomilast significantly decreased RV16-induced ICAM-1 expression to approximately 45% (p < 0.01). CXCL8 protein/mRNA production was reduced by about 41% (p < 0.05), whereas IL-6 protein/mRNA production was increased to between 41-81% (p < 0.001). There was a trend to reduction by cilomilast of RV16-induced CCL5. Conclusions: Cilomilast has differential effects on RV16-induced ICAM-1 and interleukins, inhibiting virus-induced ICAM-1 expression and CXCL8 while increasing IL-6 production. These in vitro effects may help to explain the beneficial actions of this PDE4 inhibitor in vivo.

Citation

Zhu, J., Edwards, M. R., Message, S. D., Stanciu, L. A., Johnston, S. L., & Jeffery, P. K. (2024). Cilomilast Modulates Rhinovirus-Induced Airway Epithelial ICAM-1 Expression and IL-6, CXCL8 and CCL5 Production. Pharmaceuticals (Basel, Switzerland), 17(11), 1554. https://doi.org/10.3390/ph17111554

DOI

10.3390/ph17111554

URI

https://hdl.handle.net/20.500.14709/159

Usage rights

CC BY 4.0

License

https://creativecommons.org/licenses/by/4.0/