| Title : Implication of S-adenosylhomocysteine hydrolase in inhibition of TNF-alpha- and IL-1beta-induced expression of inflammatory mediators by AICAR in RPE cells - Qin_2008_Invest.Ophthalmol.Vis.Sci_49_1274 |
| Author(s) : Qin S , Ni M , De Vries GW |
| Ref : Invest Ophthalmol Vis Sci , 49 :1274 , 2008 |
| Abstract : PURPOSE: AMP-activated protein kinase (AMPK) has been suggested to be a novel signaling pathway in regulating inflammation. The role of AMPK in retinal pigment epithelial cell inflammatory response is addressed using AMPK activator 5-aminoimidazole-4-carboxamide riboside (AICAR). METHODS: Protein expression and activation of signaling molecules were detected by immunoblotting. Cytokines were determined by ELISA kits. AMPKalpha expression was knockdown by siRNAs. RESULTS: AICAR inhibited tumor necrosis factor (TNF)-alpha- or interleukin (IL)-1beta-induced production of IL-6, IL-8, and monocyte chemotactic protein (MCP)-1 and of intercellular adhesion molecule (ICAM)-1 expression in human RPE cells. The inhibitory effect on cytokine production and ICAM-1 expression persisted in the RPE cells in which AMPK was knocked down by AMPK siRNA. Moreover, an adenosine kinase inhibitor 5'-iodotubercidin, which effectively abolished AMPK activation caused by AICAR, did not reverse the anti-inflammatory effect of AICAR. In comparison, anti-inflammatory effects of AICAR were mimicked by adenosine but not inosine, the metabolites of AICAR. Finally, with the exception of TNF-alpha-induced IL-6 production, adenosine dialdehyde, an inhibitor of S-adenosylhomocysteine hydrolase, was found to block cytokine production and ICAM-1 expression. CONCLUSIONS: Regardless of the ability of AICAR to activate AMPK, the inhibitory effects of AICAR on cytokine production and ICAM-1 expression were not associated with AMPK. The mechanism of AICAR inhibition may be attributed to the interference of adenosylmethionine-dependent methylation. |
| ESTHER : Qin_2008_Invest.Ophthalmol.Vis.Sci_49_1274 |
| PubMedSearch : Qin_2008_Invest.Ophthalmol.Vis.Sci_49_1274 |
| PubMedID: 18326758 |
Qin S, Ni M, De Vries GW (2008)
Implication of S-adenosylhomocysteine hydrolase in inhibition of TNF-alpha- and IL-1beta-induced expression of inflammatory mediators by AICAR in RPE cells
Invest Ophthalmol Vis Sci
49 :1274
Qin S, Ni M, De Vries GW (2008)
Invest Ophthalmol Vis Sci
49 :1274