Premium
The role of adenosine receptors in regulating production of tumour necrosis factor‐α and chemokines by human lung macrophages
Author(s) -
Buenestado A,
Grassin Delyle S,
Arnould I,
Besnard F,
Naline E,
BlouquitLaye S,
Chapelier A,
Bellamy JF,
Devillier P
Publication year - 2010
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00614.x
Subject(s) - adenosine a3 receptor , adenosine a2b receptor , adenosine a1 receptor , adenosine , adenosine receptor , medicine , agonist , endocrinology , receptor , ccpa , receptor antagonist , chemistry , pharmacology , biology , antagonist
Background and purpose: Adenosine is a major endogenous regulator of macrophage function, and activates four specific adenosine receptors (A 1 , A 2A , A 2B and A 3 ). Here, we have assessed in human lung macrophages the modulation of the expression of adenosine receptor mRNA by lipopolysaccharide (LPS), and the relative contributions of the different adenosine receptors to LPS‐induced production of tumour necrosis factor (TNF)‐α and chemokines. Experimental approach: Lung macrophages isolated from resected lungs were stimulated with LPS and treated with adenosine receptor agonists or/and antagonists. Adenosine receptor expression was assessed with qRT‐PCR. Cytokines were measured in lung macrophage supernatants with elisa . Key results: LPS increased (about 400‐fold) mRNA for A 2A adenosine receptors, decreased mRNA for A 1 and A 2B , but had no effect on A 3 adenosine receptor mRNA. The adenosine receptor agonist NECA inhibited TNF‐α production concentration dependently, whereas the A 1 receptor agonist, CCPA, and the A 3 receptor agonist, AB‐MECA, inhibited TNF‐α production only at concentrations affecting A 2A receptors. NECA also inhibited the production of CCL chemokines (CCL2, CCL3, CCL4, CCL5) and CXCL chemokines (CXCL9 and CXCL10), but not that of CXCL1, CXCL8 and CXCL5. Reversal of NECA‐induced inhibition of TNF‐α and chemokine production by the selective A 2A adenosine receptor antagonist ZM 241385, but not the A 2B receptor antagonist, MRS 1754, or the A 3 receptor antagonist, MRS 1220, indicated involvement of A 2A receptors. Conclusions and implications: LPS up‐regulated A 2A adenosine receptor gene transcription, and this receptor subtype mediated inhibition of the LPS‐induced production of TNF‐α and of a subset of chemokines in human lung macrophages.