Interleukin-7 stimulates secretion of S100A4 by activating the JAK/STAT signaling pathway in human articular chondrocytes.
Interleukin-7 stimulates secretion of S100A4 by activating the JAK/STAT signaling pathway in human articular chondrocytes.
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DOI：
10.1002/art.24295
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发表时间：
2009-03
影响因子：
--
通讯作者：
Loeser, Richard F.
中科院分区：
文献类型：
--
作者：
Yammani, Raghunatha R.;Long, David;Loeser, Richard F.
S100 A4已被证明在OA软骨中增加，并通过激活晚期糖基化终末产物（AGEs）受体刺激软骨细胞产生MMP-13。本研究的目的是了解软骨细胞分泌S100 A4的机制。用10 ng/ml的IL-1β、IL-6、IL-7或IL-8刺激从踝关节软骨分离的人关节软骨细胞。用JAK-3抑制剂、布雷菲德菌素-A或放线菌酮预处理细胞。使用磷酸特异性抗体的免疫印迹来确定信号蛋白的活化。通过免疫印迹法测量条件培养基中S100 A4的分泌，通过ELISA测量MMP-13。在用IL-6或IL-8处理后观察到S100 A4的软骨细胞分泌，但在用等量IL-7处理的培养物中更大，而用IL-1β处理时未观察到。IL-7激活JAK/STAT途径，JAK-3和STAT-3的磷酸化增加，导致S100 A4和MMP-13的产生增加。过表达显性负性MMP-13构建体抑制IL-7介导的MMP-13的产生。用JAK-3抑制剂或放线菌酮预处理软骨细胞可阻断IL-7介导的S100 A4分泌。然而，用布雷菲德菌素-A预处理软骨细胞没有。IL-7通过激活JAK/STAT信号刺激软骨细胞分泌S100 A4，然后S100 A4以自分泌方式起作用，通过分泌刺激MMP-13产生。由于IL-7和S100 A4在OA软骨中均上调，并可刺激软骨细胞产生MMP-13，因此该信号通路可能有助于OA发展期间的软骨破坏。
S100A4 has been shown to be increased in OA cartilage and to stimulate chondrocytes to produce MMP-13 through activation of the receptor for advanced glycation end products (RAGE). The aim of this study was to understand the mechanism of S100A4 secretion by chondrocytes. Human articular chondrocytes isolated from ankle cartilage were stimulated with 10ng/ml of IL-1β, IL-6, IL-7 or IL-8. Cells were pretreated with either a JAK-3 inhibitor, brefeldin-A, or cycloheximide. Immunoblotting with phospho-specific antibodies was used to determine the activation of signaling proteins. Secretion of S100A4 was measured in the conditioned media by immunoblotting and MMP-13 was measured by ELISA. Chondrocyte secretion of S100A4 was observed after treatment with IL-6 or IL-8 but was much greater in cultures treated with equal amounts of IL-7 and was not observed with IL-1β. IL-7 activated the JAK/STAT pathway with increased phosphorylation of JAK-3 and STAT-3 leading to increased production of S100A4 and MMP-13. Overexpression of a dominant negative RAGE construct inhibited IL-7 mediated production of MMP-13. Pretreatment of chondrocytes with a JAK-3 inhibitor or with cycloheximide blocked the IL-7 mediated secretion of S100A4. However, pretreatment of chondrocytes with brefeldin-A did not. IL-7 stimulates chondrocyte secretion of S100A4 via activation of JAK/STAT signaling and then S100A4 acts in an autocrine manner to stimulate MMP-13 production via RAGE. Since both IL-7 and S100A4 are upregulated in OA cartilage and can stimulate MMP-13 production by chondrocytes, this signaling pathway could contribute to cartilage destruction during the development of OA.
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影响因子：
--
作者：
Loeser, RF;Yammani, R;Yan, SD
通讯作者：
Yan, SD
影响因子：
10.5
作者：
Miyazaki, T;Takaoka, A;Taniguchi, T
通讯作者：
Taniguchi, T
影响因子：
8
作者：
Ambartsumian, N;Klingelhöfer, J;Lukanidin, E
通讯作者：
Lukanidin, E
人类关节软骨细胞产生IL-7并对IL-7作出反应，而基质金属蛋白酶13的产生增加。
影响因子：
4.9
作者：
Long, David;Blake, Simon;Song, Xiao-Yu;Lark, Michael;Loeser, Richard F.
通讯作者：
Loeser, Richard F.
影响因子：
--
作者：
Forsyth, CB;Pulai, J;Loeser, RF
通讯作者：
Loeser, RF