Up-regulation by tumor necrosis factor alpha of intercellular adhesion molecule 1 expression and function in synovial fibroblasts and its inhibition by glucocorticoids.
Up-regulation by tumor necrosis factor alpha of intercellular adhesion molecule 1 expression and function in synovial fibroblasts and its inhibition by glucocorticoids.
复制标题
肿瘤坏死因子 α 上调滑膜成纤维细胞中细胞间粘附分子 1 的表达和功能及其受糖皮质激素的抑制。
DOI：
10.1002/art.1780361107
复制
发表时间：
1993
影响因子：
--
通讯作者：
S. McColl
中科院分区：
文献类型：
--
作者：
P. Tessier;M. Audette;P. Cattaruzzi;S. McColl
目的
目的：研究肿瘤坏死因子α（TNF α）对体外培养的人滑膜成纤维细胞细胞间粘附分子1（ICAM 1）基因表达的影响，并探讨地塞米松对ICAM 1基因表达的调节作用。
方法
细胞表面ICAM-1的表达通过流式细胞术、酶免疫测定法和免疫沉淀法测定。北方印迹法检测ICAM-1 mRNA水平。通过测量单核细胞与滑膜成纤维细胞的粘附来确定ICAM-1功能。
结果
ICAM-1在未刺激细胞上的表达较弱，但在暴露于TNF α后以时间和剂量依赖性方式迅速增强。通过北方印迹法测定，用TNF α处理细胞还导致稳态ICAM-1 mRNA水平的时间和剂量依赖性增加。放线菌酮和放线菌素D可抑制ICAM-1的表达。类风湿和非类风湿关节病患者的滑膜成纤维细胞对TNF α的反应相似。粘附研究表明，ICAM-1参与外周血单核细胞与TNF α激活的滑膜成纤维细胞的粘附。此外，地塞米松抑制TNF α诱导的ICAM-1的表面表达、ICAM-1 mRNA的积累以及单核细胞与TNF α激活的滑膜成纤维细胞的粘附。
结论
这些综合结果提供了ICAM-1在炎性滑膜炎中的重要作用以及糖皮质激素抑制作用的潜在新位点的进一步证据。
OBJECTIVE
To examine the regulation of the intercellular adhesion molecule 1 (ICAM-1) gene in cultured human synovial fibroblasts in response to tumor necrosis factor alpha (TNF alpha), and investigate its modulation by the synthetic glucocorticoid, dexamethasone.
METHODS
Cell surface expression of ICAM-1 was determined by flow cytometry, enzyme immunoassay, and immunoprecipitation. ICAM-1 messenger RNA (mRNA) levels were monitored by Northern blot. ICAM-1 function was determined by measuring the adhesion of monocytes to synovial fibroblasts.
RESULTS
ICAM-1 expression on unstimulated cells was weak but was rapidly enhanced in both a time- and dose-dependent manner following exposure to TNF alpha. Treatment of the cells with TNF alpha also resulted in both a time- and dose-dependent increase in steady-state ICAM-1 mRNA levels, as determined by Northern blot. The increased expression of ICAM-1 was inhibited by cycloheximide and actinomycin D. Cultured synovial fibroblasts from patients with rheumatoid and nonrheumatoid arthropathies responded similarly to TNF alpha. Adhesion studies demonstrated that ICAM-1 is involved in the adherence of peripheral blood monocytes to TNF alpha-activated synovial fibroblasts. In addition, dexamethasone inhibited TNF alpha-induced surface expression of ICAM-1, accumulation of ICAM-1 mRNA, and adhesion of monocytes to TNF alpha-activated synovial fibroblasts.
CONCLUSION
These combined results provide further evidence of an important role of ICAM-1 in inflammatory synovitis, as well as a potentially novel site of antiinflammatory action of glucocorticoids.
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影响因子：
4.4
作者：
Michael Loran Dustin;R. Rothlein;A. Bhan;C. Dinarello;T. Springer
通讯作者：
Michael Loran Dustin;R. Rothlein;A. Bhan;C. Dinarello;T. Springer
影响因子：
15.9
作者：
CRONSTEIN, BN;LEVIN, RI;HIRSCHHORN, R
通讯作者：
HIRSCHHORN, R
影响因子：
4.4
作者：
G. Firestein;J. Álvaro-Gracia;R. Maki
通讯作者：
G. Firestein;J. Álvaro-Gracia;R. Maki
影响因子：
4.4
作者：
N. Mukaida;C. Zachariae;G. Gusella;Koji Matsushima
通讯作者：
N. Mukaida;C. Zachariae;G. Gusella;Koji Matsushima
糖皮质激素对基因表达的调节。
影响因子：
18.2
作者：
Burnstein,KL;Cidlowski,JA
通讯作者：
Cidlowski,JA