6533b830fe1ef96bd1297aea

RESEARCH PRODUCT

Cilomilast counteracts the effects of cigarette smoke in airway epithelial cells.

Mark GjomarkajCarina Gabriela UasufGiuseppe LiottaAntonino GiarratanoStefania La GruttaElisabetta PaceMalcolm JohnsonMaria Ferraro

subject

MAPK/ERK pathwayCyclohexanecarboxylic AcidsLymphocyteImmunologyCyclohexanecarboxylic AcidRespiratory MucosaBiologyCell LineSmokeparasitic diseasesNitrilesmedicineHumansLymphocytesCOPDChemotaxisCilomilastInterleukin-8ChemotaxiChemotaxisTobacco Use Disordermedicine.diseaseNeutrophiliaChemokine CXCL10Toll-Like Receptor 4medicine.anatomical_structureGene Expression RegulationPhosphodiesterase 4 InhibitorImmunologyTLR4PhosphorylationLymphocytePhosphodiesterase 4 Inhibitorsmedicine.symptomNitrileHumanmedicine.drugSignal Transduction

description

Abstract Cigarette smoke extracts (CSE) alter TLR4 expression and activation in bronchial epithelial cells. Cilomilast, a phosphodiesterase-4 inhibitor, inhibits cigarette smoke-induced neutrophilia. This study was aimed to explore whether cilomilast, in a human bronchial epithelial cell line (16-HBE), counteracted CSE effects. In particular, TLR4 expression, IP-10 and IL-8 release, lymphocyte and neutrophil chemotactic activity and ERK and IkBa phosphorylation in CSE and LPS-stimulated 16-HBE were assessed. CSE increased TLR4 expression, reduced IP-10 release and lymphocyte chemotactic activity and increased IL-8 release and neutrophil chemotactic activity. Cilomilast reduced TLR4 expression, IL-8 release and neutrophil chemotactic activity as well as it increased IP-10 release and lymphocyte chemotactic activity. All these cilomilast mediated effects were associated with a reduced ERK1/2 and with an increased IkBa phosphorylation. In conclusion, the present study provides compelling evidences that cilomilast may be considered a possible valid therapeutic option in controlling inflammatory processes present in smokers.

yearjournalcountryeditionlanguage
2010-08-12Cellular immunology
10.1016/j.cellimm.2011.02.004https://pubmed.ncbi.nlm.nih.gov/21382614