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Inhibition of TNF-alpha secretion from peripheral
blood monocular cells by triptolid is associated with TNF-alpha-308
gene polymorphisms in rheumatoid arthritis patients |
Xiu-Liang TAO MM,Sheng-Hao TU MD,Ri-Bo XIONG MM,Yong-Hong HU BM, |
Department of Integrated
Traditional Chinese and Western Medicine, Tongji Hospital, Tongji
Medical College, Huazhong University of Science and Technology, Wuhan
430030, China; |
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Abstract This study examined the inhibitory effect of triptolid (TP) on tumor necrosis factor-α (TNF-α) secreted from peripheral blood monocular cells (PBMCs) and the association of the inhibitory effect with TNF-α-308 gene polymorphisms in rheumatoid arthritis (RA) patients. Gene polymorphism at A-G site 308 in the promoter region of TNF-α gene was detected in 42 RA patients by using allele specific polymerase chain reaction (AS-PCR) assay. PBMCs were harvested from these patients and treated first with lipopolysaccharides (LPS) and then with different doses of TP (1, 5.4 and 15 ng/mL). The TNF-α level in the supernatants was measured by enzyme-linked immunosorbent assay (ELISA). The results showed that TNF-α level in the supernatants of TP (1 ng/mL)-treated PBMCs was decreased by 3.80% and 4.91%, respectively, in the patients with AA and AG genotypes, when compared with those treated with LPS alone (P>0.05). Moreover, the TNF-α level in the patients with GG genotype was reduced by 20.74% (P<0.05). When PBMCs were treated with TP at 5.4 ng/mL, TNF-α levels in the patients with AA, AG, and GG genotypes were decreased by 20.42%, 34.73%, and 41.69%, respectively (P<0.05). The TNF-α level was slightly higher in the PBMCs treated with 15 ng/mL of TP than those in the two TP groups in the patients carrying AA, AG, and GG genotypes (P>0.05). It was concluded that gene polymorphism at TNF-α-308 sites may relate to the secretion of TNF-α in RA patients. TP has different inhibitory effects on the secretion of TNF-α in the patients harboring different genotypes, which may be one of the reasons for individual variation in response to TP.
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Keywords
arthritis, rheumatoid
molonuclear cells
tumor necrosis factor
gene polymorphisms
triptolid
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Issue Date: 05 June 2010
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