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dc.creatorStamatiou, R.en
dc.creatorParaskeva, E.en
dc.creatorBoukas, K.en
dc.creatorGourgoulianis, K. I.en
dc.creatorMolyvdas, P. A.en
dc.creatorHatziefthimiou, A. A.en
dc.date.accessioned2015-11-23T10:48:29Z
dc.date.available2015-11-23T10:48:29Z
dc.date.issued2009
dc.identifier10.1183/09031936.00089407
dc.identifier.issn0903-1936
dc.identifier.urihttp://hdl.handle.net/11615/33342
dc.description.abstractAzithromycin is used in long-term, low-dose treatment of airway diseases where airway wall remodelling is present. Since it improves total score symptom and respiratory function of such patients, we hypothesise that azithromycin's additional clinical benefits are due to an inhibition of airway smooth muscle cell (SMC) proliferation. Rabbit tracheal SMCs were treated with azithromycin (10(-5) to 10(-6) M) in the presence or absence of 10% fetal bovine serum (FBS). The proliferation was estimated using the Cell Titer 96 (R) AQ(ueous), One Solution Assay (Promega, Madison, WI, USA). Cell viability was assessed with Trypan blue staining and flow cytometry after 7-aminoactinomycin D (7-AAD) staining. Induction of autophagy was studied by indirect immmunofluorescence and/or Western blotting with antibodies against human smooth muscle a-actin, beclin 1, light chain 3 and caspase 3. The involvement of the phosphoinositide 3-kinase pathway was investigated with the inhibitors LY294002 and wortmannin. Incubation with azithromycin for 72 h in the presence of FBS reduced SMC proliferation and viability in a dose-dependent manner. Azithromycin treatment was accompanied by the formation of cytoplasmic vacuoles, characteristic of autophagy. All these effects were reversible after azithromycin removal and prevented by the autophagy inhibitor, 3-methyladenine, or LY294002, but not by wortmannin. In conclusion, azithromycin reduces proliferation and causes autophagy of airway SMCs.en
dc.source.uri<Go to ISI>://WOS:000269702800025
dc.subjectAirway smooth muscle cellsen
dc.subjectautophagyen
dc.subjectazithromycinen
dc.subjectproliferationen
dc.subjectLASER FLOW-CYTOMETRYen
dc.subjectBRONCHIAL HYPERRESPONSIVENESSen
dc.subjectMACROLIDEen
dc.subjectANTIBIOTICSen
dc.subjectINDUCED APOPTOSISen
dc.subjectMCF-7 CELLSen
dc.subjectIN-VIVOen
dc.subjectERYTHROMYCINen
dc.subjectDEATHen
dc.subjectASTHMAen
dc.subjectINHIBITORen
dc.subjectRespiratory Systemen
dc.titleAzithromycin has an antiproliferative and autophagic effect on airway smooth muscle cellsen
dc.typejournalArticleen


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