IL-4 inhibition of IL-1 induced Matrix metalloproteinase-3 (MMP-3) expression in human fibroblasts involves decreased AP-1 activation via negative crosstalk involving of Jun N-terminal kinase (JNK).
IL-4 inhibition of IL-1 induced Matrix metalloproteinase-3 (MMP-3) expression in human fibroblasts involves decreased AP-1 activation via negative crosstalk involving of Jun N-terminal kinase (JNK).
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DOI：
10.1016/j.yexcr.2013.04.010
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发表时间：
2013-06-10
影响因子：
3.7
通讯作者：
Borghaei, CRuth C.
中科院分区：
文献类型：
--
作者：
Chambers, Mariah;Kirkpatrick, Garrett;Evans, Michel;Gorski, Grzegorz;Foster, Sara;Borghaei, CRuth C.
基质金属蛋白酶-3（MMP-3）过度表达与慢性炎症背景下的组织破坏相关。已有研究表明IL-4抑制IL-1β诱导MMP-3的表达，提示AP-1可能参与了IL-4诱导MMP-3的表达。我们发现IL-1诱导的转录因子AP-1与MMP-3启动子的结合主要由c-Jun、JunB和c-Fos组成，c-Jun和c-Fos的结合受到细胞因子组合的抑制，而Jun B的结合则不受抑制。MMP-3启动子中AP-1位点的突变降低了IL-4抑制其在转染的MG-63细胞中转录的能力。蛋白质印迹法表明，两种细胞因子都能激活Jun N末端激酶（JNK），但动力学略有不同，并且两种细胞因子单独激活JNK会被联合抑制。这些结果表明，MMP-3表达的IL-4抑制与IL-1诱导的AP-1二聚体的活性形式的结合减少有关，而活性较低的含JunB的二聚体仍然存在，并表明这些变化与JNK活化减少有关。
Matrix metalloproteinase-3 (MMP-3) over-expression is associated with tissue destruction in the context of chronic inflammation. Previous studies showed that IL-4 inhibits induction of MMP-3 by IL-1β, and suggested that AP-1 might be involved. Here we show that IL-1 induced binding of transcription factor AP-1 to the MMP-3 promoter consists primarily of c-Jun, JunB, and c-Fos and that binding of c-Jun and c-Fos is inhibited by the combination of cytokines while binding of Jun B is not. Mutation of the AP-1 site in the MMP-3 promoter decreased the ability of IL-4 to inhibit its transcription in transfected MG-63 cells. Western blotting showed that both cytokines activate Jun N-terminal kinase (JNK), but with somewhat different kinetics, and that activation of JNK by both cytokines individually is inhibited by the combination. These results indicate that IL-4 inhibition of MMP-3 expression is associated with reduction of IL-1 induced binding of active forms of the AP-1 dimer, while less active JunB-containing dimers remain, and suggest that these changes are associated with decreased activation of JNK.
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影响因子：
4
作者：
Hess, J;Angel, P;Schorpp-Kistner, M
通讯作者：
Schorpp-Kistner, M
影响因子：
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作者：
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