title: AMP-activated protein kinase activation by 5-aminoimidazole-4-carbox-amide-1-β-D-ribofuranoside (AICAR) reduces lipoteichoic acid-induced lung inflammation.
abstract: Adenosine monophosphate-activated protein (AMP)-activated kinase (AMPK) is a highly conserved kinase that plays a key role in energy homeostasis. Activation of AMPK was shown to reduce inflammation in response to lipolysaccharide in vitro and in vivo. 5-Aminoimidazole-4-carbox-amide-1-β-D-ribofuranoside (AICAR) is intracellularly converted to the AMP analog ZMP, which activates AMPK. Lipoteichoic acid (LTA) is a major component of the cell wall of Gram-positive bacteria that can trigger inflammatory responses. In contrast to lipopolysaccharide, little is known on the effects of AMPK activation in LTA-triggered innate immune responses. Here, we studied the potency of AMPK activation to reduce LTA-induced inflammation in vitro and in lungs in vivo. Activation of AMPK in vitro reduced cytokine production in the alveolar macrophage cell line MH-S. In vivo, AMPK activation reduced LTA-induced neutrophil influx, as well as protein leak and cytokine/chemokine levels in the bronchoalveolar space. In conclusion, AMPK activation inhibits LTA-induced lung inflammation in mice.
authors: Center for Infection and Immunity Amsterdam, 1105 AZ Amsterdam, The Netherlands. a.j.hoogendijk@amc.uva.nl
authors: Arie J
authors: AJ
authors: Hoogendijk
authors: Sandra S
authors: SS
authors: Pinhanços
authors: Tom
authors: T
authors: van der Poll
authors: Catharina W
authors: CW
authors: Wieland
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D007004:Hypoglycemic Agents / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D012265:Ribonucleotides / Q000494:pharmacology*; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018925:Chemokines; D007004:Hypoglycemic Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012265:Ribonucleotides; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; D000620:Aminoimidazole Carboxamide; C009900:lipoteichoic acid; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; C031143:AICA ribonucleotide