Adenosine stimulates CREB activation in macrophages via a p38 MAPK-mediated mechanism

Zoltán H. Németh, S. Joseph Leibovich, Edwin A. Deitch, Beáta Sperlágh, László Virág, E. Sylvester Vizi, Csaba Szabó, György Haskó

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Adenosine is an endogenously released autocoid that has potent receptor-mediated modulatory effects on macrophage function. The intracellular pathways mediating these effects are incompletely understood. Since adenosine receptor occupancy has been associated with activation of the cAMP-PKA system as well as of p38 MAPK and p42/44 MAPK, all of which can activate the CREB transcription factor system, we hypothesized that adenosine would activate CREB in macrophages. Using RAW 264.7 macrophages, we found that extracellular adenosine enhanced CREB transcriptional activity and increased phosphorylation of nuclear CREB. On the other hand, adenosine failed to alter CREB DNA binding. Adenosine stimulated both p38 and p42/44 MAPK activation. The p38 MAPK pathway inhibitor SB203580 but not the p42/44 MAPK pathway blocker PD98059 decreased adenosine-induced CREB activation, indicating that p38 MAPK but not p42/44 MAPK is an upstream mediator of CREB activation. Thus, some of the immunomodulatory effects of adenosine in macrophages may be explained by its augmenting effect on CREB activation.

Original languageEnglish (US)
Pages (from-to)883-888
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number4
StatePublished - Dec 26 2003
Externally publishedYes


  • Antigen
  • Cytokine
  • Interleukin
  • Monocyte
  • Nuclear factor-κB
  • Phagocytosis
  • Purinergic
  • Purinoceptor
  • Receptor
  • Toll-like receptor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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