5-Aminoimidazole-4-Carboxamide-1-β-4-Ribofuranoside Inhibits Proinflammatory Response in Glial Cells: A Possible Role of AMP-Activated Protein Kinase

• DOI: 10.1523/jneurosci.4288-03.2004
• Publication Date: 2004-01-14T19:04:08Z
• Authors: Shailendra Giri; Narendra Nath; Brian Smith; Benoit Viollet; Avtar K. Singh; Inderjit Singh
• Keywords: Proinflammatory cytokine; AMP-Activated Protein Kinase

AMP-activated protein kinase (AMPK) is tightly regulated by the cellular AMP:ATP ratio and plays a central role in regulation of energy homeostasis metabolic stress. A pharmacological activator AMPK, 5-amino-4-imidazole carboxamide riboside (AICAR) inhibited lipopolysaccharide (LPS)-induced expression proinflammatory cytokines (tumor necrosis factor α, interleukin-1β, interleukin-6) inducible nitric oxide synthase primary rat astrocytes, microglia, peritoneal macrophages. AICAR attenuates LPS-induced activation nuclear κB via downregulation IκB α/β activity. It also inhibits translocation CCAAT/enhancer-binding (C/EBP) transcription inhibiting C/EBP-δ brain glial cells. The dominant negative form AMPKα 2 (D157A) its antisense documents possible AMPK process. production inflammatory mediators serum their CNS rats injected with sublethal dose LPS intraperitoneal injection. These observations cultured cells as well animal model suggest that may be therapeutic value treating diseases.