AICAR stimulates IL-6 production via p38 MAPK in cardiac fibroblasts in adult mice: a possible role for AMPK

Biochem Biophys Res Commun. 2005 Dec 2;337(4):1139-44. doi: 10.1016/j.bbrc.2005.09.174. Epub 2005 Oct 6.


Though known as a sensor of energy balance, AMP-activated protein kinase (AMPK) was recently shown to limit damage and apoptotic activity and contribute to the late preconditioning in heart. Interleukin-6 was also reported to involve in anti-apoptosis and cardio-protection in myocardium. Interestingly, both AMPK activity and IL-6 level were increased in response to ischemia, hypertrophy and oxidative stress. To determine whether AMPK activation will promote IL-6 production, cardiac fibroblasts (CFs) from mice were incubated with AMPK activator, 5-aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR). The results demonstrated that AICAR time and dose-dependently stimulated IL-6 production by ELISA and immunofluorescence. Pretreatment with p38 mitogen-activated protein kinase (MAPK) inhibitor blocked AICAR-induced IL-6 production; furthermore, AICAR-activated p38 MAPK phosphorylation by Western blot. To confirm that the increase in IL-6 production is ascribed to AMPK activation, we used another known AMPK activator, metformin. It also dose-dependently potentiated IL-6 production in CFs, and this potentiation could be reversed by p38 MAPK inhibitor. In conclusion, AMPK activation promoted IL-6 production in CFs via p38 MAPK-dependent pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Aging / physiology*
  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Cells, Cultured
  • Enzyme Activation / drug effects
  • Fibroblasts
  • Interleukin-6 / biosynthesis*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Multienzyme Complexes / metabolism*
  • Myocardium / cytology*
  • Myocardium / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Ribonucleotides / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Interleukin-6
  • Multienzyme Complexes
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • Protein-Serine-Threonine Kinases
  • p38 Mitogen-Activated Protein Kinases
  • AMP-Activated Protein Kinases
  • AICA ribonucleotide