Classical macrophage activation up-regulates several matrix metalloproteinases through mitogen activated protein kinases and nuclear factor-κB.
Classical macrophage activation up-regulates several matrix metalloproteinases through mitogen activated protein kinases and nuclear factor-κB.
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DOI：
10.1371/journal.pone.0042507
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Newby AC
中科院分区：
文献类型：
--
作者：
Huang WC;Sala-Newby GB;Susana A;Johnson JL;Newby AC
基质金属蛋白酶（MMPs）对细胞外基质（ECM）和细胞表面的重塑是单核细胞和巨噬细胞的重要功能。最近的研究强调了经典活化和选择性活化巨噬细胞的不同作用，但MMPs及其抑制剂的调节尚未得到全面研究。体外未分离CD16+/−或负选择CD16−巨噬细胞的经典活化上调MMP-1、-3、-7、-10、-12、-14和-25，并降低TIMP-3稳态mRNA水平。细菌脂多糖、IL-1和tnf - α比干扰素γ更有效，但对MMP-25和TIMP-3的影响除外。相比之下，替代激活降低了MMP-2、-8和-19，但增加了MMP -11、-12、-25和TIMP-3的稳态mRNA水平。经典活化过程中MMPs的上调依赖于丝裂原活化蛋白激酶、磷酸肌苷-3激酶和κB激酶-2抑制剂。干扰素γ对janus激酶-2依赖性的影响。在研究中，蛋白质浓度和胶原酶活性也有类似的影响。此外，体内人类动脉粥样硬化斑块中MMP-1和-10的活性与经典激活标记共定位。综上所述，巨噬细胞经典活化在体外和体内选择性上调几种MMPs并下调TIMP-3，而选择性活化上调一组不同的MMPs和TIMP-3。这里定义的信号通路提示了选择性调节MMP活性的目标。
Remodelling of the extracellular matrix (ECM) and cell surface by matrix metalloproteinases (MMPs) is an important function of monocytes and macrophages. Recent work has emphasised the diverse roles of classically and alternatively activated macrophages but the consequent regulation of MMPs and their inhibitors has not been studied comprehensively. Classical activation of macrophages derived in vitro from un-fractionated CD16+/− or negatively-selected CD16− macrophages up-regulated MMP-1, -3, -7, -10, -12, -14 and -25 and decreased TIMP-3 steady-state mRNA levels. Bacterial lipopolysaccharide, IL-1 and TNFα were more effective than interferonγ except for the effects on MMP-25, and TIMP-3. By contrast, alternative activation decreased MMP-2, -8 and -19 but increased MMP -11, -12, -25 and TIMP-3 steady-state mRNA levels. Up-regulation of MMPs during classical activation depended on mitogen activated protein kinases, phosphoinositide-3-kinase and inhibitor of κB kinase-2. Effects of interferonγ depended on janus kinase-2. Where investigated, similar effects were seen on protein concentrations and collagenase activity. Moreover, activity of MMP-1 and -10 co-localised with markers of classical activation in human atherosclerotic plaques in vivo. In conclusion, classical macrophage activation selectively up-regulates several MMPs in vitro and in vivo and down-regulates TIMP-3, whereas alternative activation up-regulates a distinct group of MMPs and TIMP-3. The signalling pathways defined here suggest targets for selective modulation of MMP activity.
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影响因子：
4.4
作者：
Martinez, Fernando O.;Gordon, Siamon;Mantovani, Alberto
通讯作者：
Mantovani, Alberto
DOI：
10.1006/bbrc.1999.1551
发表时间：
1999-10-22
影响因子：
3.1
作者：
Bond, M;Baker, AH;Newby, AC
通讯作者：
Newby, AC
影响因子：
10.8
作者：
Bond, M;Chase, AJ;Newby, AC
通讯作者：
Newby, AC
影响因子：
14.5
作者：
Bar-Or, A;Nuttall, RK;Yong, VW
通讯作者：
Yong, VW
影响因子：
4.9
作者：
Andreas, Kristin;Luebke, Carsten;Sittinger, Michael
通讯作者：
Sittinger, Michael