Role of AMP-Activated Protein Kinase (AMPK) in Smoking-Induced Lung Inflammation and Emphysema

Abstract

BackgroundAMP-activated protein kinase (AMPK) not only functions as an intracellular energy sensor and regulator, but is also a general sensor of oxidative stress. Furthermore, there is recent evidence that it participates in limiting acute inflammatory reactions, apoptosis and cellular senescence. Thus, it may oppose the development of chronic obstructive pulmonary disease.MethodsTo investigate the role of AMPK in cigarette smoke-induced lung inflammation and emphysema we first compared cigarette smoking and polyinosinic-polycytidylic acid [poly(I:C)]-induced lung inflammation and emphysema in AMPKα1-deficient (AMPKα1-HT) mice and wild-type mice of the same genetic background. We then investigated the role of AMPK in the induction of interleukin-8 (IL-8) by cigarette smoke extract (CSE) in A549 cells.ResultsCigarette smoking and poly(I:C)-induced lung inflammation and emphysema were elevated in AMPKα1-HT compared to wild-type mice. CSE increased AMPK activation in a CSE concentration- and time-dependent manner. 5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR), an AMPK activator, decreased CSE-induced IL-8 production while Compound C, an AMPK inhibitor, increased it, as did pretreatment with an AMPKα1-specific small interfering RNA.ConclusionAMPKα1-deficient mice have increased susceptibility to lung inflammation and emphysema when exposed to cigarette smoke, and AMPK appears to reduce lung inflammation and emphysema by lowering IL-8 production.

Progranulin protects lung epithelial cells from cigarette smoking‐induced apoptosis

“…important risk factor for COPD. 3,4 Emphysema is characterized by irreversible alveolar wall destruction. It has been proposed that the underlying mechanism resulting in the irreversible airway damage of COPD is closely linked to the apoptosis of endothelial and epithelial cells, which is associated with increased oxidative stress and infiltration of activated neutrophils and macrophages.…”

“…COPD is predicted to become the third leading cause of death by 2020 . Cigarette smoke (CS) is the most important risk factor for COPD . Emphysema is characterized by irreversible alveolar wall destruction.…”

Kinases as Novel Therapeutic Targets in Asthma and Chronic Obstructive Pulmonary Disease

“…2/2 mice have reduced emphysema after cigarette smoke exposure, indicating that activation of this pathway has therapeutic potential in asthma and COPD (Lee et al, 2015). Flavones, such as quercitin, and resveratrol also activate AMPK.…”

β-Arrestin2 Inhibits Expression of Inflammatory Cytokines in BEAS-2B Lung Epithelial Cells Treated with Cigarette Smoke Condensate via Inhibition of Autophagy

“…A previous study showed that exposure to cigarette smoke increased the phosphorylation of AMPK in primary culture of cerebral endothelial cells in the C57BL/6 mouse [43]. Exposure to cigarette smoke has been shown to increase AMPK activation in the lungs in a CSC concentration-dependent and timedependent manner [54]. A recent study also showed that the activation of mTOR suppressed airway inflammation and emphysema induced by cigarette smoke via the inhibition of autophagy and cell death [55].…”