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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

Increased cigarette smoking- and poly(I:C)-induced lung inflammation and emphysema in AMPKα1-deficient (AMPKα1-HT) mice. (A) Histological assessment at 2 months of lung sections stained with hematoxylin and eosin (×100). (B) Total bronchoalveolar lavage cell counts and differential cell counts. (C) Morphometric analysis of mean linear intercepts. AMPK: AMP-activated protein kinase; WC: wild-type no smoke (n=4); HC: AMPKα1-HT no smoke (n=5); WS: wild-type exposed to smoke (n=4); HS: AMPKα1-HT exposed to smoke (n=5). Data represent mean±SEM. * and † denotes significant differences (p<0.05) between the WC and WS group, and between the WS and HS group, respectively.Figure 3.
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Figure 2: Increased cigarette smoking- and poly(I:C)-induced lung inflammation and emphysema in AMPKα1-deficient (AMPKα1-HT) mice. (A) Histological assessment at 2 months of lung sections stained with hematoxylin and eosin (×100). (B) Total bronchoalveolar lavage cell counts and differential cell counts. (C) Morphometric analysis of mean linear intercepts. AMPK: AMP-activated protein kinase; WC: wild-type no smoke (n=4); HC: AMPKα1-HT no smoke (n=5); WS: wild-type exposed to smoke (n=4); HS: AMPKα1-HT exposed to smoke (n=5). Data represent mean±SEM. * and † denotes significant differences (p<0.05) between the WC and WS group, and between the WS and HS group, respectively.Figure 3.

Mentions: To elucidate the role of AMPKα1 in cigarette smoke-induced lung inflammation and emphysema, AMPKα1-deficient mice were exposed to cigarette smoke or challenged with poly(I:C). The AMPKα1-deficient (AMPKα1-HT) mice produced approximately 50% of the AMPKα of wild type mice (Figure 1B). Cigarette smoke exposure and poly(I:C) treatment induced significant increases in total BAL fluid cells, and neutrophil and macrophage counts, as well as in MLI, in both wild type and AMPKα1-HT mice. However total BAL fluid cells, lymphocyte and macrophage counts, and MLI were significantly higher in the AMPKα1-HT mice than the wild type mice after exposure to cigarette smoke or poly(I:C) (Figure 2A-C).


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)

Increased cigarette smoking- and poly(I:C)-induced lung inflammation and emphysema in AMPKα1-deficient (AMPKα1-HT) mice. (A) Histological assessment at 2 months of lung sections stained with hematoxylin and eosin (×100). (B) Total bronchoalveolar lavage cell counts and differential cell counts. (C) Morphometric analysis of mean linear intercepts. AMPK: AMP-activated protein kinase; WC: wild-type no smoke (n=4); HC: AMPKα1-HT no smoke (n=5); WS: wild-type exposed to smoke (n=4); HS: AMPKα1-HT exposed to smoke (n=5). Data represent mean±SEM. * and † denotes significant differences (p<0.05) between the WC and WS group, and between the WS and HS group, respectively.Figure 3.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 2: Increased cigarette smoking- and poly(I:C)-induced lung inflammation and emphysema in AMPKα1-deficient (AMPKα1-HT) mice. (A) Histological assessment at 2 months of lung sections stained with hematoxylin and eosin (×100). (B) Total bronchoalveolar lavage cell counts and differential cell counts. (C) Morphometric analysis of mean linear intercepts. AMPK: AMP-activated protein kinase; WC: wild-type no smoke (n=4); HC: AMPKα1-HT no smoke (n=5); WS: wild-type exposed to smoke (n=4); HS: AMPKα1-HT exposed to smoke (n=5). Data represent mean±SEM. * and † denotes significant differences (p<0.05) between the WC and WS group, and between the WS and HS group, respectively.Figure 3.
Mentions: To elucidate the role of AMPKα1 in cigarette smoke-induced lung inflammation and emphysema, AMPKα1-deficient mice were exposed to cigarette smoke or challenged with poly(I:C). The AMPKα1-deficient (AMPKα1-HT) mice produced approximately 50% of the AMPKα of wild type mice (Figure 1B). Cigarette smoke exposure and poly(I:C) treatment induced significant increases in total BAL fluid cells, and neutrophil and macrophage counts, as well as in MLI, in both wild type and AMPKα1-HT mice. However total BAL fluid cells, lymphocyte and macrophage counts, and MLI were significantly higher in the AMPKα1-HT mice than the wild type mice after exposure to cigarette smoke or poly(I:C) (Figure 2A-C).

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