The role of adenosine receptors in regulating production of tumour necrosis factor-alpha and chemokines by human lung macrophages.
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Buenestado A, Grassin Delyle S, Arnould I, Besnard F, Naline E, Blouquit-Laye S, Chapelier A, Bellamy JF, Devillier P
The role of adenosine receptors in regulating production of tumour necrosis factor-alpha and chemokines by human lung macrophages.
Br J Pharmacol. 2010 Mar;159(6):1304-11. doi: 10.1111/j.1476-5381.2009.00614.x. Epub 2010 Feb 5.
- PubMed ID
- 20136829 [ View in PubMed]
- Abstract
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)-alpha 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-alpha production concentration dependently, whereas the A(1) receptor agonist, CCPA, and the A(3) receptor agonist, AB-MECA, inhibited TNF-alpha 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-alpha 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-alpha and of a subset of chemokines in human lung macrophages.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Adenosine Adenosine receptor A1 Protein Humans YesAgonistDetails Adenosine Adenosine receptor A2a Protein Humans YesAgonistDetails Adenosine Adenosine receptor A2b Protein Humans YesAgonistDetails Adenosine Adenosine receptor A3 Protein Humans YesAgonistDetails