title: Involvement of purinergic system in the release of cytokines by macrophages exposed to glioma-conditioned medium.
abstract: Macrophages are involved in cancer progression. M1 macrophages have an antitumor effect, whereas M2 phenotype are associated with tumor growth. The progression of gliomas involves the participation of an inflammatory microenvironment. Adenosine triphosphate (ATP) can act as pro-inflammatory signal, whereas adenosine has opposite properties. The biological effects of extracellular nucleotides/nucleosides mediated by purinergic receptors are controlled by ectonucleotidases. In the present work, we evaluated whether glioma-conditioned medium (GL-CM) modulates macrophage differentiation and the participation of ATP and adenosine in the release of pro-and anti-inflammatory cytokines by these cells. The results show that macrophages exposed to GL-CM were modulated to an M2-like phenotype. HPLC analysis of GL-CM demonstrated the presence of significant amounts of ATP and its metabolites. Macrophages exposed to GL-CM presented decreased ATP and AMP hydrolysis and increased IL-10 and MCP-1 secretion, effects that were diminished by P1 or P2 antagonists. GL-CM did not alter the release of IL-6 by macrophages, although treatment with ATP promoted an increase in the release of IL-6, which was prevented by a P2X7 antagonist. In summary, we found that A2A and P2X7 activation is necessary for IL-10, MCP-1, and IL-6 release by macrophages exposed to GL-CM, which, in turn, modulates the macrophages to M2-phenotype. The present study establishes a relationship between M2-like polarization, cytokine release and purinergic receptor activation in macrophages exposed to GL-CM. Therefore, the data presented herein contributes to advancing in the field of cancer-related inflammation and point specific purinergic receptors as targets for modulation of the phenotype of glioma-associated macrophages.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básica da Saúde, UFRGS, Porto Alegre, RS, Brasil.
authors.forename: Letícia Scussel
authors.initials: LS
authors.lastname: Bergamin
authors.forename: Elizandra
authors.initials: E
authors.lastname: Braganhol
authors.forename: Fabrício
authors.initials: F
authors.lastname: Figueiró
authors.forename: Emerson André
authors.initials: EA
authors.lastname: Casali
authors.forename: Rafael Fernandes
authors.initials: RF
authors.lastname: Zanin
authors.forename: Jean
authors.initials: J
authors.lastname: Sévigny
authors.forename: Ana Maria Oliveira
authors.initials: AM
authors.lastname: Battastini
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000378:metabolism; D005910:Glioma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism*; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D011983:Receptors, Purinergic / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D015850:Interleukin-6; D010446:Peptide Fragments; D043705:Receptor, Adenosine A2A; D011983:Receptors, Purinergic; D058486:Receptors, Purinergic P2X7; C508645:monocyte chemoattractant protein 1 (66-77); D016753:Interleukin-10; D000255:Adenosine Triphosphate; D000241:Adenosine
keywords: CONDITIONED MEDIUM; GLIOMA; MACROPHAGES; PURINERGIC SYSTEM