Gene interactions and pathways from curated databases and text-mining
J Neurosci 2004, PMID: 14724246

5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside inhibits proinflammatory response in glial cells: a possible role of AMP-activated protein kinase.

Giri, Shailendra; Nath, Narendra; Smith, Brian; Viollet, Benoit; Singh, Avtar K; Singh, Inderjit

AMP-activated protein kinase (AMPK) is tightly regulated by the cellular AMP:ATP ratio and plays a central role in the regulation of energy homeostasis and metabolic stress. A pharmacological activator of AMPK, 5-amino-4-imidazole carboxamide riboside (AICAR) inhibited lipopolysaccharide (LPS)-induced expression of proinflammatory cytokines (tumor necrosis factor alpha, interleukin-1beta, and interleukin-6) and inducible nitric oxide synthase in primary rat astrocytes, microglia, and peritoneal macrophages. AICAR attenuates the LPS-induced activation of nuclear factor kappaB via downregulation of IkappaB kinase alpha/beta activity. It also inhibits nuclear translocation of CCAAT/enhancer-binding protein (C/EBP) transcription factor by inhibiting the expression of C/EBP-delta in brain glial cells. The dominant negative form of AMPKalpha2 (D157A) and its antisense documents a possible role of AMPK in the regulation of the cellular proinflammatory process. AICAR also inhibited the production of inflammatory mediators in serum and their expression in CNS of rats injected with a sublethal dose of LPS by intraperitoneal injection. These observations in cultured cells as well as in the animal model suggest that AICAR may be of therapeutic value in treating inflammatory diseases.

Diseases/Pathways annotated by Medline MESH: Inflammation
Document information provided by NCBI PubMed

Text Mining Data

interleukin-1beta ⊣ AMPK: " A pharmacological activator of AMPK , 5-amino-4-imidazole carboxamide riboside ( AICAR ) inhibited lipopolysaccharide (LPS) induced expression of proinflammatory cytokines ( tumor necrosis factor alpha, interleukin-1beta , and interleukin-6 ) and inducible nitric oxide synthase in primary rat astrocytes, microglia, and peritoneal macrophages "

interleukin-1beta ⊣ AMPK: " A pharmacological activator of AMPK , 5-amino-4-imidazole carboxamide riboside ( AICAR ) inhibited lipopolysaccharide (LPS) induced expression of proinflammatory cytokines ( tumor necrosis factor alpha, interleukin-1beta , and interleukin-6 ) and inducible nitric oxide synthase in primary rat astrocytes, microglia, and peritoneal macrophages "

interleukin-6 ⊣ AMPK: " A pharmacological activator of AMPK , 5-amino-4-imidazole carboxamide riboside ( AICAR ) inhibited lipopolysaccharide (LPS) induced expression of proinflammatory cytokines ( tumor necrosis factor alpha, interleukin-1beta, and interleukin-6 ) and inducible nitric oxide synthase in primary rat astrocytes, microglia, and peritoneal macrophages "

nitric oxide synthase ⊣ AMPK: " A pharmacological activator of AMPK , 5-amino-4-imidazole carboxamide riboside ( AICAR ) inhibited lipopolysaccharide (LPS) induced expression of proinflammatory cytokines ( tumor necrosis factor alpha, interleukin-1beta, and interleukin-6 ) and inducible nitric oxide synthase in primary rat astrocytes, microglia, and peritoneal macrophages "

interleukin-1beta → lipopolysaccharide (LPS): " A pharmacological activator of AMPK, 5-amino-4-imidazole carboxamide riboside ( AICAR ) inhibited lipopolysaccharide (LPS) induced expression of proinflammatory cytokines ( tumor necrosis factor alpha, interleukin-1beta , and interleukin-6 ) and inducible nitric oxide synthase in primary rat astrocytes, microglia, and peritoneal macrophages "

interleukin-1beta → lipopolysaccharide (LPS): " A pharmacological activator of AMPK, 5-amino-4-imidazole carboxamide riboside ( AICAR ) inhibited lipopolysaccharide (LPS) induced expression of proinflammatory cytokines ( tumor necrosis factor alpha, interleukin-1beta , and interleukin-6 ) and inducible nitric oxide synthase in primary rat astrocytes, microglia, and peritoneal macrophages "

nitric oxide synthase → lipopolysaccharide (LPS): " A pharmacological activator of AMPK, 5-amino-4-imidazole carboxamide riboside ( AICAR ) inhibited lipopolysaccharide (LPS) induced expression of proinflammatory cytokines ( tumor necrosis factor alpha, interleukin-1beta, and interleukin-6 ) and inducible nitric oxide synthase in primary rat astrocytes, microglia, and peritoneal macrophages "

transcription factor → C/EBP-delta: " It also inhibits nuclear translocation of CCAAT/enhancer binding protein (C/EBP) transcription factor by inhibiting the expression of C/EBP-delta in brain glial cells "

Manually curated Databases

No curated data.