Lipopolysaccharide-induced expression of matrix metalloproteinases in human monocytes is suppressed by IFN-gamma via superinduction of ATF-3 and suppression of AP-1.
Lipopolysaccharide-induced expression of matrix metalloproteinases in human monocytes is suppressed by IFN-gamma via superinduction of ATF-3 and suppression of AP-1.
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DOI：
10.4049/jimmunol.181.7.5089
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发表时间：
2008-10-01
影响因子：
4.4
通讯作者：
Ivashkiv, Lionel B.
中科院分区：
文献类型：
--
作者：
Ho, Hao H.;Antoniv, Taras T.;Ji, Jong-Dae;Ivashkiv, Lionel B.
基质金属蛋白酶(MMPs)在炎症反应中被诱导，在免疫调节、血管生成、伤口愈合和组织重塑中起重要作用。MMPs的表达需要严格控制，以避免过度的组织损伤。在这项研究中，我们研究了炎症因子对原代培养的人单核细胞和巨噬细胞中基质金属蛋白酶表达的调节。干扰素γ在巨噬细胞激活因子如Toll样受体配体的作用下增加炎性细胞因子的产生，而不是广泛地抑制TLRMMPs的表达。抑制基质金属蛋白酶的表达依赖于STAT1，需要从头合成蛋白质。干扰素γ以STAT1依赖的方式显著增强转录抑制因子ATF-3的表达，这与染色质免疫沉淀检测到的ATF-3对内源性基质金属蛋白酶-1启动子的募集有关。RNA干扰实验进一步支持ATF-3在抑制基质金属蛋白酶-1表达中的作用。此外，干扰素γ抑制了AP-1转录因子对基质金属蛋白酶表达的促进作用，超转移、干扰和过表达实验表明AP-1家族成员FrA-1参与了对基质金属蛋白酶-1表达的调控。这些结果定义了干扰素γ介导的动态环，该环限制了与炎症相关的组织损伤的可能性，并确定了在炎症环境中调节髓系细胞基质金属蛋白酶表达的转录因子。
Matrix metalloproteinases (MMPs) are induced during inflammatory responses and are important for immune regulation, angiogenesis, wound healing and tissue remodeling. Expression of MMPs needs to be tightly controlled to avoid excessive tissue damage. In this study we investigated the regulation of MMP expression by inflammatory factors in primary human monocytes and macrophages. IFNγ, which augments inflammatory cytokine production in response to macrophage-activating factors such as Toll-like receptor (TLR) ligands, instead broadly suppressed TLR-induced MMP expression. Inhibition of MMP expression was dependent on STAT1 and required de novo protein synthesis. IFNγ strongly enhanced TLR-induced expression of the transcriptional repressor ATF-3 in a STAT1-dependent manner, which correlated with recruitment of ATF-3 to the endogenous MMP-1 promoter as detected by chromatin immunoprecipitation assays. RNA interference experiments further supported a role for ATF-3 in suppression of MMP-1 expression. In addition, IFNγ suppressed DNA binding by AP-1 transcription factors that are known to promote MMP expression and a combination of supershift, RNA interference and overexpression experiments implicated AP-1 family member Fra-1 in the regulation of MMP-1 expression. These results define an IFNγ-mediated homeostatic loop that limits the potential for tissue damage associated with inflammation, and identify transcriptional factors that regulate MMP expression in myeloid cells in inflammatory settings.
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DOI：
10.1073/pnas.48.6.1014
发表时间：
1962-01-01
影响因子：
11.1
作者：
GROSS, J;LAPIERE, CM
通讯作者：
LAPIERE, CM
影响因子：
30.5
作者：
Corry, DB;Rishi, K;Kheradmand, F
通讯作者：
Kheradmand, F
侵袭性黑色素瘤细胞中胶原酶1（MMP-1）的过表达是由ERK通路介导的--： BRAF 突变和成纤维细胞生长因子信号的作用
影响因子：
4.8
作者：
Huntington, JT;Shields, JM;Brinckerhoff, CE
通讯作者：
Brinckerhoff, CE
DOI：
10.1016/0167-4889(89)90085-2
发表时间：
1989-07-11
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
ANDREWS, HJ;BUNNING, RAD;RUSSELL, RGG
通讯作者：
RUSSELL, RGG
表皮生长因子诱导最大胶原酶-1（MMP-1）和 T24 膀胱癌细胞恶性特征需要 STAT3 激活
影响因子：
8
作者：
Itoh, M;Murata, T;Yoshida, K
通讯作者：
Yoshida, K