Up-regulation of vascular endothelial growth factor expression by adenosine through adenosine A2 receptors in the rat tongue treated with endotoxin.
Archives of Oral Biology(2009)
Abstract
The main focus of the present investigation is to evaluate a differential effect of adenosine on the up-regulation of vascular endothelial growth factor (VEGF) expression through adenosine A2 receptors in the rat tongue treated with endotoxin (lipopolysaccharide: LPS). Angiogenesis in the rat tongue treated with LPS/incomplete Freund's adjuvant (IFA) or endotoxin/IFA/adenosine A2 receptor (A2R) antagonists was examined using immunohistochemistry for LYVE-1, ED1, ED2, OX6, langerin and VEGF, and real-time polymerase chain reaction (PCR) for VEGF. The distributional density of both blood vessels and OX6+ cells was significantly increased at day 8 after injection of LPS/IFA. The immunoreactive products of VEGF were intensely labelled in the cytoplasm of various antigen presenting cells (APCs) including dendritic cells (DCs) with double-immunofluorescence technique. Increase in VEGF mRNA expression level, the occupancy ratio of blood vessels, and the number of ED1+, ED2+, OX6+, and langerin+ cells was inhibited in the injured tongue of rats as a consequence of the treatment with A2R antagonists. The present results indicate that the LPS-induced adenosine might promote angiogenesis by the up-regulation of VEGF expression in macrophages/DCs through A2 receptors. This suggests that the synergistic interaction between toll-like receptor (TLR) and A2 receptor signalling observed in vivo plays an important role in oral mucosal wound healing.
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Key words
LPS,IFA,VEGF,APCs,DCs,PLP,MHC,TLR,TNF-α,IL,ZM 241385,MRS 1754 hydrate,NECA,CGS21680,bFGF,TP
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