Effect of curcumin (Curcuma longa extract) on LPS-induced acute lung injury is mediated by the activation of AMPK.
OBJECTIVE
Curcumin, a biphenolic compound extracted from turmeric (Curcuma longa), possesses potent anti-inflammatory activity. The present study investigated whether curcumin could increase 5' adenosine monophosphate-activated protein kinase (AMPK) activity in macrophages and modulate the severity of lipopolysaccharide (LPS)-induced acute lung injury.


METHODS
Macrophages were treated with curcumin and then exposed (or not) to LPS. Acute lung injury was induced by intratracheal administration of LPS in BALB/c mice.


RESULTS
Curcumin increased phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), a downstream target of AMPK, in a time- and concentration-dependent manner. Curcumin did not increase phosphorylation of liver kinase B1, a primary kinase upstream of AMPK. STO-609, an inhibitor of calcium(2+)/calmodulin-dependent protein kinase kinase, diminished curcumin-induced AMPK phosphorylation, but transforming growth factor-beta-activated kinase 1 inhibitor did not. Curcumin also diminished the LPS-induced increase in phosphorylation of inhibitory κB-alpha and the production of tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein (MIP)-2, and interleukin (IL)-6 by macrophages. Systemic administration of curcumin significantly decreased the production of TNF-α, MIP-2, and IL-6 as well as neutrophil accumulation in bronchoalveolar lavage fluid, and also decreased pulmonary myeloperoxidase levels and the wet/dry weight ratio in mice subjected to LPS treatment.


CONCLUSIONS
These results suggest that the protective effect of curcumin on LPS-induced acute lung injury is associated with AMPK activation.
Departments of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital, 5 Hak dong, Gwangju, 501-746, Korea.
Joungmin
J
Kim
Departments of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital, 5 Hak dong, Gwangju, 501-746, Korea.
Seong-Wook
SW
Jeong
Departments of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital, 5 Hak dong, Gwangju, 501-746, Korea.|Research Institute of Medical Sciences, Chonnam National University, Gwangju, Korea.
Hui
H
Quan
Departments of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital, 5 Hak dong, Gwangju, 501-746, Korea.
Cheol-Won
CW
Jeong
Departments of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital, 5 Hak dong, Gwangju, 501-746, Korea.
Jeong-Il
JI
Choi
Departments of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital, 5 Hak dong, Gwangju, 501-746, Korea. nextphil2@jnu.ac.kr.|Research Institute of Medical Sciences, Chonnam National University, Gwangju, Korea. nextphil2@jnu.ac.kr.
Hong-Beom
HB
Bae
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D055371:Acute Lung Injury / Q000188:drug therapy*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D054426:Chemokine CXCL2 / Q000378:metabolism; D030024:Curcuma / Q000737:chemistry*; D003474:Curcumin / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053644:Naphthalimides / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D001562:Benzimidazoles; D054426:Chemokine CXCL2; D008070:Lipopolysaccharides; D053644:Naphthalimides; C458525:STO 609; D014409:Tumor Necrosis Factor-alpha; D055372:AMP-Activated Protein Kinases; D003474:Curcumin
AMPK; CaMKK; Curcumin; LPS; Macrophage