Up-regulation of vascular endothelial growth factor expression by adenosine through adenosine A2 receptors in the rat tongue treated with endotoxin.
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 A(2) 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 A(2) receptor (A(2)R) 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 A(2)R antagonists. The present results indicate that the LPS-induced adenosine might promote angiogenesis by the up-regulation of VEGF expression in macrophages/DCs through A(2) receptors. This suggests that the synergistic interaction between toll-like receptor (TLR) and A(2) receptor signalling observed in vivo plays an important role in oral mucosal wound healing.
Hara
Yaiko
Y
Department of Anatomy II, Tsurumi University School of Dental Medicine, Tsurumi-ku, Yokohama 230-8501, Japan.
Kuroda
Noriyuki
N
Inoue
Kouji
K
Sato
Tetsuji
T
D000241:Adenosine / Q000502:physiology*; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D005928:Glossitis / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D043683:Receptors, Adenosine A2 / Q000096:biosynthesis*; D013047:Specific Pathogen-Free Organisms; D014059:Tongue / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D058917:Adenosine A2 Receptor Antagonists; D008070:Lipopolysaccharides; D043683:Receptors, Adenosine A2; D042461:Vascular Endothelial Growth Factor A; D000241:Adenosine