5-Aminoimidazole-4-carboxamide riboside suppresses lipopolysaccharide- induced TNF-α production through inhibition of phosphatidylinositol 3-kinase/Akt activation in RAW 264.7 murine macrophages

Bong Sook Jhun, Quanri Jin, Young Taek Oh, Sung Soo Kim, Yoon Kong, Yong Ho Cho, Joohun Ha, Hyung Hwan Baik, Insug Kang

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96 Scopus citations

Abstract

5-Aminoimidazole-4-carboxamide riboside (AICAR) is an adenosine analog and a widely used activator of AMP-activated protein kinase (AMPK). We examined the effect of AICAR on LPS-induced TNF-α production in RAW 264.7 and peritoneal macrophages and its molecular mechanism in RAW 264.7 macrophages. Treatment with AICAR inhibited LPS-induced increases in TNF-α mRNA and protein levels in these cells. AICAR or LPS did not alter the AMPK activity as well as the phosphorylations of AMPK α (Thr172) and ACC (Ser79). Moreover, an adenosine kinase inhibitor 5-iodotubercidin enhanced the suppressive effect of AICAR on TNF-α levels. These results suggest that the effect of AICAR on TNF-α suppression in RAW 264.7 cells is independent of AMPK activation. In addition, an adenosine receptor antagonist 8-SPT had no effect on AICAR-induced suppression of TNF-α levels. Finally, we observed that AICAR inhibited LPS-induced activation of PI 3-kinase and Akt, whereas it had no effect on the activation of p38 and ERK1/2. Taken together, these results suggest that the anti-inflammatory action of AICAR in RAW 264.7 macrophages is independent of AMPK activation and is associated with inhibition of LPS-induced activation of PI 3-kinase/Akt pathway.

Original languageEnglish (US)
Pages (from-to)372-380
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume318
Issue number2
DOIs
StatePublished - May 28 2004
Externally publishedYes

Bibliographical note

Funding Information:
We thank Dr. S. Park (Kyung Hee University, Korea) for assistance with real-time RT-PCR analysis. This work was supported by grants from Korean Ministry of Health and Welfare (02-PJ1-PG10-20904-0001) and from Korea Science and Engineering Foundation (R13-2002-020-01001-0).

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