Tumour necrosis factor-alpha induces hyperreactivity in tracheal smooth muscle of the guinea-pig in vitro.

Tumour necrosis factor-alpha induces hyperreactivity in tracheal smooth muscle of the guinea-pig in vitro.
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肿瘤坏死因子-α 在体外诱导豚鼠气管平滑肌的高反应性。

DOI:
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发表时间:
1998
影响因子:
24.3
通讯作者:
E. Wouters
E. Wouters
中科院分区:
医学1区
文献类型:
--
作者:
H. Pennings;K. Kramer;A. Bast;W. Buurman;E. Wouters

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Recent studies have implicated a role for tumour necrosis factor-alpha (TNFalpha) in the development of the asthmatic reaction. In this study, we examined the influence of TNFalpha on isotonic contraction of tracheal smooth muscle of the guinea-pig in vitro in response to methacholine. Tracheal rings were incubated with recombinant human (rh)TNFalpha (3x10(-11) M) for 30 min, and concentration-response curves to methacholine before and after incubation with rhTNFalpha were compared with the control. The present study demonstrates that rhTNFalpha increases maximal isotonic contraction of tracheal smooth muscle to methacholine (mean+/-SEM 169.6+/-43%, p<0.005). This effect was observed only after a 30 min delay between incubation and methacholine challenge testing. Experiments with 10(-13) - 10(-10) M rhTNF-alpha yielded similar results at all concentrations used. The effects of rhTNFalpha (10(-11) M) on tracheal hyperreactivity could be completely inhibited by coincubation with dimeric rTNF-receptor-p80 construct (10(-10) M) (p<0.01). In order to analyse secondary mediator release, experiments using coincubation with indomethacin (10(-5) M) and WEB 2086 (10(-6) M), a specific platelet activating factor (PAF) antagonist, demonstrated that the effect of rhTNFalpha on tracheal rings was mediated by PAF, since WEB 2086 completely inhibited rhTNFalpha-induced hyperreactivity (p<0.05). In conclusion, this study demonstrates that recombinant human tumour necrosis factor-alpha induces hyperreactivity in tracheal smooth muscle in vitro, which was shown to be mediated by platelet activating factor. Our study emphasizes the role of tumour necrosis factor-alpha in the pathophysiology of bronchial hyperresponsiveness.
DOI: 10.1056/nejm198806093182301
发表时间: 1988-06-09
影响因子: 158.5
作者:
MICHIE, HR;MANOGUE, KR;WILMORE, DW
通讯作者: WILMORE, DW
用 IL-1-β、肿瘤坏死因子或 IFN-γ 刺激的人单核细胞合成双相血小板激活因子。
DOI: --
发表时间: 1988
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
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DOI: --
发表时间: 1991
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
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发表时间: 1992-05-01
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发表时间: 1996-06-15
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