title: Effect of cigarette smoke and dexamethasone on Hsp72 system of alveolar epithelial cells.
abstract: Smoking is the leading risk factor of chronic obstructive pulmonary disease (COPD) and lung cancer. Corticosteroids are abundantly used in these patients; however, the interaction of smoking and steroid treatment is not fully understood. Heat shock proteins (Hsps) play a central role in the maintenance of cell integrity, apoptosis and cellular steroid action. To better understand cigarette smoke-steroid interaction, we examined the effect of cigarette smoke extract (CSE) and/or dexamethasone (DEX) on changes of intracellular heat shock protein-72 (Hsp72) in lung cells. Alveolar epithelial cells (A549) were exposed to increasing doses (0; 0.1; 1; and 10 μM/μl) of DEX in the medium in the absence(C) and presence of CSE. Apoptosis, necrosis, Hsp72 messenger-ribonucleic acid (mRNA) and protein expression of cells were measured, and the role of Hsp72 on steroid effect examined. CSE reduced the number of viable cells by significantly increasing the number of apoptotic and necrotic cells. DEX dose-dependently decreased the ratio of apoptosis when CSE was administered, without change in necrosis. CSE - DEX co-treatment dose-dependently increased Hsp72 mRNA and protein expression, with the highest level measured in CSE + DEX (10) cells, while significantly lower levels were noted in all respective C groups. Pretreatment with Hsp72 silencing RNA confirmed that increased survival observed following DEX administration in CSE-treated cells was mainly mediated via the Hsp72 system. CSE significantly decreases cell survival by inducing apoptosis and necrosis. DEX significantly increases Hsp72 mRNA and protein expression only in the presence of CSE resulting in increased cellular protection and survival. DEX exerts its cell protective effects by decreasing apoptotic cell death via the Hsp72 system in CSE-treated alveolar epithelial cells.
authors.affiliation: Department of Pulmonology, Semmelweis University Budapest, Hungary. galkrisztina@gmail.com
authors.forename: Krisztina
authors.initials: K
authors.lastname: Gál
authors.forename: Aron
authors.initials: A
authors.lastname: Cseh
authors.forename: Balázs
authors.initials: B
authors.lastname: Szalay
authors.forename: Krisztina
authors.initials: K
authors.lastname: Rusai
authors.forename: Adám
authors.initials: A
authors.lastname: Vannay
authors.forename: József
authors.initials: J
authors.lastname: Lukácsovits
authors.forename: Uwe
authors.initials: U
authors.lastname: Heemann
authors.forename: Attila J
authors.initials: AJ
authors.lastname: Szabó
authors.forename: György
authors.initials: G
authors.lastname: Losonczy
authors.forename: Lilla
authors.initials: L
authors.lastname: Tamási
authors.forename: Veronika
authors.initials: V
authors.lastname: Müller
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D019610:Cytoprotection; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D020868:Gene Silencing; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009336:Necrosis / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D014026:Nicotiana / Q000009:adverse effects*
chemical_list: D050884:HSP72 Heat-Shock Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012906:Smoke; D003907:Dexamethasone