AMP-activated protein kinase activation by 5-aminoimidazole-4-carbox-amide-1-β-D-ribofuranoside (AICAR) reduces lipoteichoic acid-induced lung inflammation.

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.