Effect of anti-inflammatory drugs on the NF-kappaB activation of HEK293 cells / 药学学报
Acta Pharmaceutica Sinica
; (12): 513-517, 2005.
Article
em Zh
| WPRIM
| ID: wpr-353483
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>AIM</b>To investigate the regulatory effects of various anti-inflammatory drugs on both endogenous and TNFalpha-induced NF-kappaB activation as well as the relative biological activity.</p><p><b>METHODS</b>HEK293 cells were cultured in 96-well plate and 6-well plate, treated with meloxicam, indomethacin, dexamethasone and hydrocortisone, without or with 10 ng.mL(-1) TNFalpha for 24 hours. Then cell proliferation was measured by MTT and cell apoptosis was analyzed by pI stain-flow cytometry. HEK293/ kappaB-luc cells transfected stably with pElam-kappaB-luc vector, were cultured in 96-well plate and treated as above. Equal amounts of cell lysates were tested for luciferase activity which represents NF-kappaB activation.</p><p><b>RESULTS</b>Endogenous NF-kappaB activation was present in HEK293 cells and its level can be increased about 2 times by 10 ng.mL(-1) TNFalpha-induction. Dexamethasone (1 x 10(-8) mol.L(-1)) and meloxicam (1 x 10(-7) - 1 x 10(-6) mol.L(-1)) can decrease both endogenous and TNFalpha-induced NF-kappaB activation. Hydrocortisone (1 x 10(-9) mol.L(-1)) increases endogenous NF-kappaB activation but decreases TNFalpha-induced one significantly. No influence of indomethacin on endogenous NF-kappaB activation was observed. However, its influence on TNFalpha-induced NF-kappaB activation is needed for further study. Cell apoptosis was observed after treatment with TNFalpha and 1 x 10(-8), 1 x 10(-6) mol.L(-1) dexamethasone and 1 x 10(-7) mol.L(-1) indomethacin, or only with dexamethasone. No significant effect of these anti-inflammatory drugs on cell proliferation was observed.</p><p><b>CONCLUSION</b>Various anti-inflammatory drugs differ in their ability to regulate NF-kappaB activation in HEK293 cells, which indicates that NF-kappaB activation might be a potential useful target to study mechanism and for drug screening.</p>
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WPRIM
Assunto principal:
Farmacologia
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Tiazinas
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Tiazóis
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Dexametasona
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Hidrocortisona
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Linhagem Celular
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Indometacina
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NF-kappa B
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Apoptose
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Biologia Celular
Limite:
Humans
Idioma:
Zh
Revista:
Acta Pharmaceutica Sinica
Ano de publicação:
2005
Tipo de documento:
Article