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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 increases the production of IL-8 in A549 cells. (A, C) Cells were exposed to 0%-4.5% CSE for 24 hours. (B, D) Cells were incubated with medium alone (time 0) or exposed to 3% CSE for the times indicated. Protein levels in cell lysates (A, B) were analyzed by Western blot, and protein levels in culture media (C, D) were analyzed by enzyme-linked immunosorbent assay. CSE: cigarette smoke extract; IL-8: interleukin 8. Data in each group are means±SEM of three independent experiments. *p<0.05, vs. 0% CSE (A, C) or time 0 (B, D).
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Figure 3: CSE increases the production of IL-8 in A549 cells. (A, C) Cells were exposed to 0%-4.5% CSE for 24 hours. (B, D) Cells were incubated with medium alone (time 0) or exposed to 3% CSE for the times indicated. Protein levels in cell lysates (A, B) were analyzed by Western blot, and protein levels in culture media (C, D) were analyzed by enzyme-linked immunosorbent assay. CSE: cigarette smoke extract; IL-8: interleukin 8. Data in each group are means±SEM of three independent experiments. *p<0.05, vs. 0% CSE (A, C) or time 0 (B, D).

Mentions: Analysis of cell lysates showed that exposure of A549 cells to various concentrations (0%, 1.5%, 3%, and 4.5%) of CSE for 24 hours increased IL-8 protein in a concentration-dependent manner (Figure 3A). CSE exposure also increased the release of IL-8 from A549 cells (Figure 3B). We chose 3% CSE as the standard CSE concentration in subsequent experiments. Exposure of A549 cells to 3% CSE increased IL-8 protein levels and release of IL-8 in a time-dependent manner (Figure 3C, D).


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 increases the production of IL-8 in A549 cells. (A, C) Cells were exposed to 0%-4.5% CSE for 24 hours. (B, D) Cells were incubated with medium alone (time 0) or exposed to 3% CSE for the times indicated. Protein levels in cell lysates (A, B) were analyzed by Western blot, and protein levels in culture media (C, D) were analyzed by enzyme-linked immunosorbent assay. CSE: cigarette smoke extract; IL-8: interleukin 8. Data in each group are means±SEM of three independent experiments. *p<0.05, vs. 0% CSE (A, C) or time 0 (B, D).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: CSE increases the production of IL-8 in A549 cells. (A, C) Cells were exposed to 0%-4.5% CSE for 24 hours. (B, D) Cells were incubated with medium alone (time 0) or exposed to 3% CSE for the times indicated. Protein levels in cell lysates (A, B) were analyzed by Western blot, and protein levels in culture media (C, D) were analyzed by enzyme-linked immunosorbent assay. CSE: cigarette smoke extract; IL-8: interleukin 8. Data in each group are means±SEM of three independent experiments. *p<0.05, vs. 0% CSE (A, C) or time 0 (B, D).
Mentions: Analysis of cell lysates showed that exposure of A549 cells to various concentrations (0%, 1.5%, 3%, and 4.5%) of CSE for 24 hours increased IL-8 protein in a concentration-dependent manner (Figure 3A). CSE exposure also increased the release of IL-8 from A549 cells (Figure 3B). We chose 3% CSE as the standard CSE concentration in subsequent experiments. Exposure of A549 cells to 3% CSE increased IL-8 protein levels and release of IL-8 in a time-dependent manner (Figure 3C, D).

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