Asbestos-induced MKP-3 expression augments TNF-alpha gene expression in human monocytes.
Asbestos-induced MKP-3 expression augments TNF-alpha gene expression in human monocytes.
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石棉诱导的 MKP-3 表达增强人单核细胞中 TNF-α 基因的表达。
DOI：
10.1165/rcmb.2007-0356oc
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发表时间：
2008
影响因子：
6.4
通讯作者：
Carter,ABrent
中科院分区：
文献类型：
--
作者：
Tephly,LindaA;Carter,ABrent
肿瘤坏死因子-α与间质纤维化的发生发展有关。我们已经证明，p38丝裂原活化蛋白(MAP)激酶调节石棉暴露的单核细胞中肿瘤坏死因子-α的表达。在这篇报道中，我们询问了细胞外信号调节激酶是否也参与了石棉暴露的单核细胞肿瘤坏死因子-α的表达。我们发现，与正常人相比，石棉肺患者肺泡巨噬细胞中p38和ERK有不同的激活。更具体地说，p38是结构性激活的，ERK激活被抑制。由于导致ERK的上游通路是完整的，我们假设ERK特异性磷酸酶在一定程度上是ERK活性降低的原因。我们评估了暴露于石棉后是否增加了在肺中高表达并特异性地去磷酸化ERK的双特异性磷酸酶-MKP-3。我们发现，暴露于石棉后，MKP-3的表达增加，并且其表达受p38调控。我们发现p38和ERK相互负调控，而MKP-3在这种差异激活中起作用。我们还发现p38是肿瘤坏死因子-α基因表达的正调节因子，而ERK是负调节因子。高表达MKP-3的细胞中肿瘤坏死因子-α基因表达显著增加，提示石棉暴露的单核细胞产生肿瘤坏死因子-α所必需的环境是有利于p38丝裂原活化的环境。综上所述，这些数据表明，p38MAPK通过激活暴露于石棉的人单核细胞中的MKP-3来增强肿瘤坏死因子-α基因的表达，从而下调ERK。
TNF-α is associated with the development of interstitial fibrosis. We have demonstrated that the p38 mitogen-activated protein (MAP) kinase regulates TNF-α expression in monocytes exposed to asbestos. In this report, we asked if extracellular signal–regulated kinase (ERK) was also involved in TNF-α expression in monocytes exposed to asbestos. We found that p38 and ERK were differentially activated in alveolar macrophages obtained from patients with asbestosis compared with normal subjects. More specifically, p38 was constitutively active and ERK activation was suppressed. Since the upstream pathway leading to ERK was intact, we hypothesized that an ERK-specific phosphatase was, in part, responsible for the decreased ERK activity. We evaluated whether the dual specificity phosphatase MAP kinase phosphatase (MKP)-3, which is highly expressed in the lung and specifically dephosphorylates ERK, was increased after exposure to asbestos. We found that MKP-3 increased after exposure to asbestos, and its expression was regulated by p38. We found that p38 and ERK negatively regulated one another, and MKP-3 had a role in this differential activation. We also found that p38 was a positive regulator and ERK was a negative regulator of TNF-α gene expression. Cells overexpressing MKP-3 had a significant increase in TNF-α gene expression, suggesting than an environment favoring p38 MAP kinase activation is necessary for TNF-α production in monocytes exposed to asbestos. Taken together, these data demonstrate that the p38 MAP kinase down-regulates ERK via activation of MKP-3 in human monocytes exposed to asbestos to enhance TNF-α gene expression.
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接触石棉的工人炎症细胞介质的临床相关性。
DOI：
10.1164/ajrccm/148.1.68
发表时间：
1993
期刊：
The American review of respiratory disease
影响因子：
--
作者：
Schwartz,DA;Galvin,JR;Frees,KL;Dayton,CS;Burmeister,LF;Merchant,JA;Hunninghake,GW
通讯作者：
Hunninghake,GW
DOI：
10.1152/ajplung.1998.275.2.l389
发表时间：
1998-08
期刊：
American journal of physiology. Lung cellular and molecular physiology
影响因子：
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作者：
M. Monick;A. B. Carter;G. Gudmundsson;L. Geist;G. Hunninghake
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M. Monick;A. B. Carter;G. Gudmundsson;L. Geist;G. Hunninghake
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影响因子：
4.4
作者：
A. Hance;S. Douches;R. Winchester;V. Ferrans;R. Crystal
通讯作者：
R. Crystal
DOI：
10.1016/s0021-9258(18)53507-9
发表时间：
1993-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
D. Robbins;E. Zhen;H. Owaki;C. Vanderbilt;D. Ebert;T. Geppert;M. Cobb
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D. Robbins;E. Zhen;H. Owaki;C. Vanderbilt;D. Ebert;T. Geppert;M. Cobb
蛋白激酶 C 激活的花生四烯酸代谢减少伴随着大鼠肺中巨噬细胞的分化。
DOI：
--
发表时间：
1990
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Peters-Golden,M;McNish,RW;Brieland,JK;Fantone,JC
通讯作者：
Fantone,JC