title: Cigarette smoke alters cell cycle and induces inflammation in lung fibroblasts.
abstract: BACKGROUND
  Lung fibroblasts are crucial for the integrity of alveolar structure. Cigarette smoking, the major risk factor for chronic obstructive pulmonary disease, impairs the repair functions of lung fibroblasts.
  
  
  OBJECTIVE
  The study simultaneously assessed for the first time cell cycle, p53, p21, p38, ERK 1/2 and IL-8.
  
  
  METHODS
  Primary foetal lung fibroblasts (HFL-1) and primary lung fibroblasts from former (n = 5) and current (n = 5) smokers with/without cigarette smoke extracts (CSEs) and inhibitors of p38 and ERK1/2 were studied for cell cycle events and for marker expression by flow-cytometry, western-blot analysis and ELISA.
  
  
  RESULTS
  CSE exposure did not induce caspase 3 cleavage or DNA laddering but reduced S phase, and increased G1 and G2/M in HFL-1. Furthermore CSE increased: p53 and p21 expression; p38 and ERK 1/2 pathway activation; and IL-8 release. Inhibitors of p38 and ERK 1/2 reversed the effects of CSE on cell cycle and on IL-8 release. ERK 1/2 inhibitor was able to reverse the effects of CSE on p21 expression. Primary lung fibroblasts from current smokers had higher ERK 1/2 activation in comparison to normal primary fibroblasts and higher percentage of cells in G1 phase and lower percentage of cells in S phase in comparison to former smoker fibroblasts.
  
  
  CONCLUSIONS
  Cigarette smoke may affect the reparative potential of lung fibroblasts altering the expression of p53 and p21 and the progression of the cell cycle to S phase. All these events are promoted by the activation of pro-inflammatory pathways.
authors: Istituto di Biomedicina e Immunologia Molecolare (I.B.I.M.), Consiglio Nazionale delle Ricerche, Palermo, Italy.
authors: C
authors: C
authors: D'Anna
authors: Istituto di Biomedicina e Immunologia Molecolare (I.B.I.M.), Consiglio Nazionale delle Ricerche, Palermo, Italy.
authors: D
authors: D
authors: Cigna
authors: Istituto di Biomedicina e Immunologia Molecolare (I.B.I.M.), Consiglio Nazionale delle Ricerche, Palermo, Italy.
authors: G
authors: G
authors: Costanzo
authors: Istituto di Biomedicina e Immunologia Molecolare (I.B.I.M.), Consiglio Nazionale delle Ricerche, Palermo, Italy.
authors: M
authors: M
authors: Ferraro
authors: Istituto di Biomedicina e Immunologia Molecolare (I.B.I.M.), Consiglio Nazionale delle Ricerche, Palermo, Italy.
authors: L
authors: L
authors: Siena
authors: Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), Palermo, Italy.
authors: P
authors: P
authors: Vitulo
authors: Istituto di Biomedicina e Immunologia Molecolare (I.B.I.M.), Consiglio Nazionale delle Ricerche, Palermo, Italy.
authors: M
authors: M
authors: Gjomarkaj
authors: Istituto di Biomedicina e Immunologia Molecolare (I.B.I.M.), Consiglio Nazionale delle Ricerche, Palermo, Italy. Electronic address: pace@ibim.cnr.it.
authors: E
authors: E
authors: Pace
mesh_terms: D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D012906:Smoke; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D048049:Extracellular Signal-Regulated MAP Kinases; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Cigarette smoke; Fibroblasts; Inflammation; Senescence