Platelet derived endothelial cell growth factor/thymidine phosphorylase enhanced human IgE production.
BACKGROUND
Angiogenesis is one pathogenesis of allergic airway disease.


METHODS
A potent angiogenic factor is platelet-derived endothelial cell growth factor (PD-ECGF), also known as thymidine phosphorylase (TP) in the field of cancer-associated research. Vascular endothelial growth factor (VEGF) is another representative angiogenic factor. Both factors were added to the culture system of human peripheral blood mononuclear cells (PBMC) with IL-4 and anti-CD40 monoclonal antibody (mAb). Total IgE levels in the supernatants and signal transduction of stimulated PBMC were evaluated.


RESULTS
Addition of PD-ECGF enhances in vitro IgE production by PBMC in the presence of IL-4 and anti-CD40 mAb, but VEGF does not enhance IgE production. Although PD-ECGF catalyzes the reversible phosphorolysis of thymidine to 2-deoxy-D-ribose-1-phosphate (2DDR), treatment of 2DDR has no effect on IgE production by human PBMC. Both IL-4 and anti-CD40 mAb induce PD-ECGF by human PBMC. Thymidine phosphorylase inhibitor (TPI), 5-chloro-6-[1- (2-iminopyrrolidinyl) methyl] uracil hydrochloride reduce IgE production via blocking of STAT6- phosphorylation.


CONCLUSIONS
Taken together, these results suggest TP involvement in the enhancement of IgE production and suggest that TPI is a novel strategy against IgE-related allergic disease.
Division of Otorhinolaryngology Head & Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Science, University of Fukui, Japan. hiya@u-fukui.ac.jp
Hideyuki
H
Yamamoto
Takechiyo
T
Yamada
Tetsuji
T
Takabayashi
Hiroshi
H
Sunaga
Myungmi
M
Oh
Norihiko
N
Narita
Akihiro
A
Kojima
Shigeharu
S
Fujieda
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D043925:Angiogenesis Inducing Agents / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000187:drug effects; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013939:Thymidine Phosphorylase / Q000378:metabolism / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D043925:Angiogenesis Inducing Agents; D004791:Enzyme Inhibitors; D050800:STAT6 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; D015847:Interleukin-4; D007073:Immunoglobulin E; D013939:Thymidine Phosphorylase