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

Overview

Journal Tuberc Respir Dis (Seoul)

Specialty Pulmonary Medicine

Date 2015 Feb 6

PMID 25653691

Citations 22

Authors

Jae Seung Lee

Sun Joo Park

You Sook Cho

Jin Won Huh

Yeon-Mok Oh

Sang-Do Lee

Affiliations

Soon will be listed here.

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.

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References

Ido Y, Carling D, Ruderman N . Hyperglycemia-induced apoptosis in human umbilical vein endothelial cells: inhibition by the AMP-activated protein kinase activation. Diabetes. 2002; 51(1):159-67. DOI: 10.2337/diabetes.51.1.159. View

Masubuchi T, Koyama S, Sato E, Takamizawa A, Kubo K, Sekiguchi M . Smoke extract stimulates lung epithelial cells to release neutrophil and monocyte chemotactic activity. Am J Pathol. 1998; 153(6):1903-12. PMC: 1866325. DOI: 10.1016/S0002-9440(10)65704-5. View

Kim T, Kim S, Moon K, Park C, Jang M, Yun E . Five-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside attenuates poly (I:C)-induced airway inflammation in a murine model of asthma. Clin Exp Allergy. 2007; 37(11):1709-19. DOI: 10.1111/j.1365-2222.2007.02812.x. View

Hellermann G, Nagy S, Kong X, Lockey R, Mohapatra S . Mechanism of cigarette smoke condensate-induced acute inflammatory response in human bronchial epithelial cells. Respir Res. 2002; 3:22. PMC: 150508. DOI: 10.1186/rr172. View

Falk J, Minai O, Mosenifar Z . Inhaled and systemic corticosteroids in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008; 5(4):506-12. PMC: 2645327. DOI: 10.1513/pats.200707-096ET. View

Huh J, Kim S, Lee J, Lee J, Van Ta Q, Kim M . Bone marrow cells repair cigarette smoke-induced emphysema in rats. Am J Physiol Lung Cell Mol Physiol. 2011; 301(3):L255-66. DOI: 10.1152/ajplung.00253.2010. View

Park C, Bang B, Kwon H, Moon K, Kim T, Lee K . Metformin reduces airway inflammation and remodeling via activation of AMP-activated protein kinase. Biochem Pharmacol. 2012; 84(12):1660-70. DOI: 10.1016/j.bcp.2012.09.025. View

Yoshida T, Tuder R . Pathobiology of cigarette smoke-induced chronic obstructive pulmonary disease. Physiol Rev. 2007; 87(3):1047-82. DOI: 10.1152/physrev.00048.2006. View

Cosio M, Saetta M, Agusti A . Immunologic aspects of chronic obstructive pulmonary disease. N Engl J Med. 2009; 360(23):2445-54. DOI: 10.1056/NEJMra0804752. View

10.

Keatings V, Collins P, Scott D, Barnes P . Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med. 1996; 153(2):530-4. DOI: 10.1164/ajrccm.153.2.8564092. View

11.

Tang G, Wang H, Wang J, Lee C, Tseng H, Wu Y . Novel role of AMP-activated protein kinase signaling in cigarette smoke induction of IL-8 in human lung epithelial cells and lung inflammation in mice. Free Radic Biol Med. 2011; 50(11):1492-502. DOI: 10.1016/j.freeradbiomed.2011.02.030. View

12.

Barnes P . Mediators of chronic obstructive pulmonary disease. Pharmacol Rev. 2004; 56(4):515-48. DOI: 10.1124/pr.56.4.2. View

13.

Kukidome D, Nishikawa T, Sonoda K, Imoto K, Fujisawa K, Yano M . Activation of AMP-activated protein kinase reduces hyperglycemia-induced mitochondrial reactive oxygen species production and promotes mitochondrial biogenesis in human umbilical vein endothelial cells. Diabetes. 2005; 55(1):120-7. View

14.

Wang Y, Liang Y, Vanhoutte P . SIRT1 and AMPK in regulating mammalian senescence: a critical review and a working model. FEBS Lett. 2010; 585(7):986-94. DOI: 10.1016/j.febslet.2010.11.047. View

15.

Lee J, Lee D, Kim E, Choe K, Oh Y, Shim T . Simvastatin inhibits cigarette smoking-induced emphysema and pulmonary hypertension in rat lungs. Am J Respir Crit Care Med. 2005; 172(8):987-93. DOI: 10.1164/rccm.200501-041OC. View

16.

Jia F, Wu C, Chen Z, Lu G . AMP-activated protein kinase inhibits homocysteine-induced dysfunction and apoptosis in endothelial progenitor cells. Cardiovasc Drugs Ther. 2011; 25(1):21-9. DOI: 10.1007/s10557-010-6277-1. View

17.

Witherden I, Vanden Bon E, Goldstraw P, Ratcliffe C, Pastorino U, Tetley T . Primary human alveolar type II epithelial cell chemokine release: effects of cigarette smoke and neutrophil elastase. Am J Respir Cell Mol Biol. 2004; 30(4):500-9. DOI: 10.1165/rcmb.4890. View

18.

Nerstedt A, Johansson A, Andersson C, Cansby E, Smith U, Mahlapuu M . AMP-activated protein kinase inhibits IL-6-stimulated inflammatory response in human liver cells by suppressing phosphorylation of signal transducer and activator of transcription 3 (STAT3). Diabetologia. 2010; 53(11):2406-16. DOI: 10.1007/s00125-010-1856-z. View

19.

Myerburg M, King Jr J, Oyster N, Fitch A, Magill A, Baty C . AMPK agonists ameliorate sodium and fluid transport and inflammation in cystic fibrosis airway epithelial cells. Am J Respir Cell Mol Biol. 2009; 42(6):676-84. PMC: 2891496. DOI: 10.1165/2009-0147OC. View

20.

Salminen A, Kaarniranta K . AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res Rev. 2011; 11(2):230-41. DOI: 10.1016/j.arr.2011.12.005. View