Cigarette smoke alters cell cycle and induces inflammation in lung fibroblasts.
Life Sci
; 126: 10-8, 2015 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-25637683
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.AIMS:
The study simultaneously assessed for the first time cell cycle, p53, p21, p38, ERK 1/2 and IL-8. MAINMETHODS:
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. KEYFINDINGS:
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.SIGNIFICANCE:
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fumaça
/
Fumar
/
Ciclo Celular
/
Sistema de Sinalização das MAP Quinases
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article