Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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Role of AMP-Activated Protein Kinase (AMPK) in Smoking-Induced Lung Inflammation and Emphysema

  • Lee, Jae Seung (Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases) ;
  • Park, Sun Joo (Department of Allergy and Clinical Immunology, Asthma Center, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Cho, You Sook (Department of Allergy and Clinical Immunology, Asthma Center, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Huh, Jin Won (Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases) ;
  • Oh, Yeon-Mok (Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases) ;
  • Lee, Sang-Do (Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases)
  • Received : 2014.07.22
  • Accepted : 2014.12.16
  • Published : 2015.01.30
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Abstract

Background: AMP-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. Methods: To 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 $AMPK{\alpha}1$-deficient ($AMPK{\alpha}1$-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. Results: Cigarette smoking and poly(I:C)-induced lung inflammation and emphysema were elevated in $AMPK{\alpha}1$-HT compared to wild-type mice. CSE increased AMPK activation in a CSE concentration- and time-dependent manner. 5-Aminoimidazole-4-carboxamide-1-${\beta}$-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 $AMPK{\alpha}1$-specific small interfering RNA. Conclusion: $AMPK{\alpha}1$-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.

Keywords

References

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