TNF-alpha and endotoxin increase hypoxia-induced VEGF production by cultured human nasal fibroblasts in synergistic fashion.
OBJECTIVE
Vascular endothelial growth factor (VEGF) promotes angiogenesis and is associated with the invasion and metastasis of malignant tumors. It enhances vascular permeability and is expressed in inflammatory nasal as well as middle-ear mucosa. As the mechanism of VEGF induction during chronic inflammation, such as chronic paranasal sinusitis (CPS) remains to be clarified, we studied the factors regulating the production of VEGF in cultured human nasal fibroblasts and discussed the role of VEGF in the pathogenesis of CPS.


METHODS
We used ELISA to quantify VEGF levels in paranasal sinus effusions, nasal secretions, and serum from patients with CPS. In addition, we cultured human nasal fibroblasts isolated from nasal polyps of CPS patients and studied the effects of hypoxia, TNF-alpha, and endotoxin on their production of VEGF using ELISA and PCR.


RESULTS
The VEGF concentration was significantly higher in paranasal sinus effusions than in nasal secretions and serum. Nasal fibroblasts produced high levels of VEGF, when cultured under hypoxic condition and this production was remarkably enhanced in the presence of TNF-alpha or endotoxin.


CONCLUSIONS
VEGF is locally produced in paranasal sinuses as well as nasal mucosa and its production is increased in patients with CPS. Hypoxia is associated with the production of VEGF by nasal fibroblasts and TNF-alpha and endotoxin may act synergistically to enhance VEGF production in paranasal sinuses under hypoxic condition.
Sun
Dong
D
Department of Otolaryngology, Field of Sensory Organology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Matsune
Shoji
S
Ohori
Junichiro
J
Fukuiwa
Tatsuya
T
Ushikai
Masato
M
Kurono
Yuichi
Y
D000704:Analysis of Variance; D016022:Case-Control Studies; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D002908:Chronic Disease; D004357:Drug Synergism; D004731:Endotoxins / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012852:Sinusitis / Q000209:etiology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D042442:Vascular Endothelial Growth Factors