Activation of adenosine A3 receptor suppresses lipopolysaccharide-induced TNF-α production through inhibition of PI 3-kinase/Akt and NF-κB activation in murine BV2 microglial cells

Jung Yeon Lee, Bong Sook Jhun, Young Taek Oh, Ju Hie Lee, Wonchae Choe, Hyung Hwan Baik, Joohun Ha, Kyung Sik Yoon, Sung Soo Kim, Insug Kang

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

Abstract

Adenosine is an endogenous nucleoside that regulates many processes, including inflammatory responses, through activation of its receptors. Adenosine receptors have been reported to be expressed in microglia, which are major immune cells of brain, yet little is known about the role of adenosine receptors in microglial cytokine production. Thus, we investigated the effect of adenosine and adenosine A3 receptor ligands on LPS-induced tumor necrosis factor (TNF-α) production and its molecular mechanism in mouse BV2 microglial cells. Adenosine and Cl-IB-MECA, a specific adenosine A 3 receptor agonist, suppressed LPS-induced TNF-α protein and mRNA levels. Moreover, MRS1523, a selective A3 receptor antagonist, blocked suppressive effects of both adenosine and Cl-IB-MECA on TNF-α. We further examined the effect of adenosine on signaling molecules, such as PI 3-kinase, Akt, p38, ERK1/2, and NF-κB, which are involved in the regulation of inflammatory responses. Adenosine inhibited LPS-induced phosphatidylinositol (PI) 3-kinase activation and Akt phosphorylation, whereas it had no effect on the phosphorylation of p38 and ERK1/2. We also found that adenosine as well as Cl-IB-MECA inhibited LPS-induced NF-κB DNA binding and luciferase reporter activity. Taken together, these results suggest that adenosine A3 receptor activation suppresses TNF-α production by inhibiting PI 3-kinase/Akt and NF-κB activation in LPS-treated BV2 microglial cells.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalNeuroscience Letters
Volume396
Issue number1
DOIs
StatePublished - Mar 20 2006
Externally publishedYes

Keywords

  • Adenosine A receptor
  • BV2 microglial cells
  • LPS
  • NF-κB
  • PI 3-kinase
  • TNF-α

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