The effect of A(2A) adenosine receptor activation on C-C chemokine receptor 7 expression in human THP1 macrophages during inflammation

Inflammation. 2012 Apr;35(2):614-22. doi: 10.1007/s10753-011-9353-1.

Abstract

C-C chemokine receptor 7 (CCR7) and its chemoattractant agonist CCL21 promote cell migration and expression of pro-inflammatory proteins in an atherogenic environment. Since A(2A) adenosine receptor activation reduces migration and inflammatory effects, we examined its effect on CCR7 expression and migration. CCR7 protein expression decreased by about a third in macrophages treated with A(2A) receptor agonist CGS 21680 (p = 0.028, n = 7) and was reversed with antagonist, although mRNA levels increased twofold (p = 0.001, n = 3). Furthermore, macrophages treated with CGS 21680 showed a significant decrease in migration (p = 0.0311, n = 7). These results suggest that A(2A) adenosine receptor activation not only modulates CCR7 expression in both normal and inflammatory environments but also regulates macrophage migration to CCR7-specific chemoattractants.

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / pharmacology
  • Adenosine A2 Receptor Agonists / pharmacology
  • Adenosine A2 Receptor Antagonists / pharmacology
  • Cell Line
  • Cell Movement / drug effects
  • Chemokine CCL21 / metabolism*
  • Humans
  • Inflammation / immunology*
  • Inflammation / metabolism
  • Macrophages / immunology*
  • Macrophages / physiology
  • Phenethylamines / pharmacology
  • RNA, Messenger / genetics
  • Receptors, Adenosine A2 / metabolism*
  • Receptors, CCR7 / metabolism*
  • Triazines / pharmacology
  • Triazoles / pharmacology

Substances

  • Adenosine A2 Receptor Agonists
  • Adenosine A2 Receptor Antagonists
  • Chemokine CCL21
  • Phenethylamines
  • RNA, Messenger
  • Receptors, Adenosine A2
  • Receptors, CCR7
  • Triazines
  • Triazoles
  • ZM 241385
  • 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
  • Adenosine