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

Lee JS, Park SJ, Cho YS, Huh JW, Oh YM, Lee SD - Tuberc Respir Dis (Seoul) (2015)

Bottom Line: Furthermore, there is recent evidence that it participates in limiting acute inflammatory reactions, apoptosis and cellular senescence.We then investigated the role of AMPK in the induction of interleukin-8 (IL-8) by cigarette smoke extract (CSE) in A549 cells.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

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 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.

Results: Cigarette 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.

Conclusion: AMPKα1-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.

No MeSH data available.


Related in: MedlinePlus

CSE activates AMPK in A549 cells. (A) Cells were incubated with medium alone or exposed to 3% CSE for the times indicated. (B) Cells were exposed to 0-10 mM AICAR (an AMPK activator) for 5 hours. (C) Cells were exposed to 0-100 µM Compound C (an AMPK inhibitor) for 5 hours. (D) Cells were transfected with various concentrations of AMPK siRNA for 48 hours. CSE: cigarette smoke extract; AMPK: AMP-activated protein kinase; AICAR: 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside.
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Figure 4: CSE activates AMPK in A549 cells. (A) Cells were incubated with medium alone or exposed to 3% CSE for the times indicated. (B) Cells were exposed to 0-10 mM AICAR (an AMPK activator) for 5 hours. (C) Cells were exposed to 0-100 µM Compound C (an AMPK inhibitor) for 5 hours. (D) Cells were transfected with various concentrations of AMPK siRNA for 48 hours. CSE: cigarette smoke extract; AMPK: AMP-activated protein kinase; AICAR: 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside.

Mentions: Exposure of A549 cells to CSE increased the phosphorylation of AMPK within 60 minutes (Figure 4A). The adenosine analog AICAR, an AMPK activator, also increased the phosphorylation of AMPK, and Compound C, an AMPK inhibitor, inhibited it (Figure 4B, C). Pretreatment with a siRNA specific for AMPK reduced AMPK protein level (Figure 4D).


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

Lee JS, Park SJ, Cho YS, Huh JW, Oh YM, Lee SD - Tuberc Respir Dis (Seoul) (2015)

CSE activates AMPK in A549 cells. (A) Cells were incubated with medium alone or exposed to 3% CSE for the times indicated. (B) Cells were exposed to 0-10 mM AICAR (an AMPK activator) for 5 hours. (C) Cells were exposed to 0-100 µM Compound C (an AMPK inhibitor) for 5 hours. (D) Cells were transfected with various concentrations of AMPK siRNA for 48 hours. CSE: cigarette smoke extract; AMPK: AMP-activated protein kinase; AICAR: 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4311035&req=5

Figure 4: CSE activates AMPK in A549 cells. (A) Cells were incubated with medium alone or exposed to 3% CSE for the times indicated. (B) Cells were exposed to 0-10 mM AICAR (an AMPK activator) for 5 hours. (C) Cells were exposed to 0-100 µM Compound C (an AMPK inhibitor) for 5 hours. (D) Cells were transfected with various concentrations of AMPK siRNA for 48 hours. CSE: cigarette smoke extract; AMPK: AMP-activated protein kinase; AICAR: 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside.
Mentions: Exposure of A549 cells to CSE increased the phosphorylation of AMPK within 60 minutes (Figure 4A). The adenosine analog AICAR, an AMPK activator, also increased the phosphorylation of AMPK, and Compound C, an AMPK inhibitor, inhibited it (Figure 4B, C). Pretreatment with a siRNA specific for AMPK reduced AMPK protein level (Figure 4D).

Bottom Line: Furthermore, there is recent evidence that it participates in limiting acute inflammatory reactions, apoptosis and cellular senescence.We then investigated the role of AMPK in the induction of interleukin-8 (IL-8) by cigarette smoke extract (CSE) in A549 cells.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

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 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.

Results: Cigarette 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.

Conclusion: AMPKα1-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.

No MeSH data available.


Related in: MedlinePlus