흡연에 의한 폐 염증과 폐기종 발생에 AMP-activated protein kinase (AMPK)의 역할 : The role of the AMP-activated protein kinase (AMPK) in the smoking induced lung inflammation and emphysema
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AMP-activated protein kinase (AMPK) is not only functions as an intracellular energy sensor and regulator, but is also a general stress sensor that is important in maintaining intracellular homoeostasis during oxidative stress. Furthermore, there is recent evidence that AMPK participates in modulating acute inflammatory reactions, apoptosis and cellular senescence. Thus, AMPK may be associated with cellular and molecular mechanisms for chronic obstructive pulmonary disease (COPD) pathogenesis. However, relatively little is known regarding function of AMPK in the lung and it is unknown yet whether and how AMPK affects the pathogenesis of COPD. In the present study, we aimed to investigate the role of AMPK in modulating cigarette smoking-induced lung inflammation and emphysema. To examine these issues, we firstly compared cigarette smoking and polyinosinic-polycytidylic acid [poly (I:C)] induced lung inflammation and emphysema between AMPKα1-deficient (AMPKα1-HT) mice and wild type mice of genetic background. Secondly, we investigated the role of AMPK in the induction of interleukin-8 (IL-8) by cigarette smoking extract (CSE) in A549 cells. Cigarette smoking and poly (I:C) induced lung inflammation and emphysema were augmented in AMPKα1-HT mice than wild type mice. CSE concentration- and time-dependently increases AMPK activation in A549 cells. 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR), an AMPK activator, significantly decreased the CSE-induced IL-8 productions and Compound C, an AMPK inhibitor, significantly increased the CSE-induced IL-8 production. Additionally, pretreatment with AMPKa1-specific small interfering RNA (siRNA) significantly increased the CSE-induced IL-8 production. In conclusion, AMPKα1-deficient mice led to increased susceptibility to lung inflammation and emphysema in response to cigarette smoking. We further provide a novel mechanistic link between AMPK and IL-8 production in A549 cells.