title: Effects of ceftaroline on the innate immune and on the inflammatory responses of bronchial epithelial cells exposed to cigarette smoke.
abstract: The tobacco smoking habit interferes with the innate host defence system against infections. Recurrent infections accelerated the functional respiratory decline. The present study assessed the effects of ceftaroline on TLR2 and TLR4 and on pro-inflammatory responses in airway epithelial cells (16HBE cell line and primary bronchial epithelial cells) with or without cigarette smoke extracts (CSE 10%). TLR2, TLR4, LPS binding and human beta defensin 2 (HBD2) were assessed by flow cytometry, NFkB nuclear translocation by western blot analysis, IL-8 and HBD2 mRNA by Real Time PCR; the localization of NFkB on the HBD2 and IL-8 promoters by ChiP Assay. CSE increased TLR4, TLR2 expression, LPS binding and IL-8 mRNA; CSE decreased HBD2 (protein and mRNA), activated NFkB and promoted the localization of NFkB on IL-8 promoter and not on HBD2 promoter. Ceftaroline counteracted the CSE effect on TLR2 expression, on LPS binding, on IL-8 mRNA, HBD2 and NFkB in 16HBE. The effects of ceftaroline on HBD2 protein and on IL-8 mRNA were confirmed in primary bronchial epithelial cells. In conclusion, ceftaroline is able to counteract the effects of CSE on the innate immunity and pro-inflammatory responses modulating TLR2, LPS binding, NFkB activation and activity, HBD2 and IL-8 expression in bronchial epithelial cells.
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Palermo, Italy. Electronic address: pace@ibim.cnr.it.
authors.forename: E
authors.initials: E
authors.lastname: Pace
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Palermo, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ferraro
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Palermo, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Di Vincenzo
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Palermo, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Siena
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Palermo, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Gjomarkaj
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D055745:Bronchioles / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001988:Bronchiolitis / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D002460:Cell Line; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002511:Cephalosporins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism / Q000633:toxicity; D016328:NF-kappa B / Q000378:metabolism; D011355:Prodrugs / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism; D000097583:Ceftaroline
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002511:Cephalosporins; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011355:Prodrugs; D014028:Tobacco Smoke Pollution; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D023083:beta-Defensins; D000097583:Ceftaroline; C508606:CXCL8 protein, human; C106641:DEFB4A protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human
keywords: Bronchial epithelial cells; Cephalosporins; Cigarette smoke; Inflammation