SR-A ligand and M-CSF dynamically regulate SR-A expression and function in primary macrophages via p38 MAPK activation.
SR-A ligand and M-CSF dynamically regulate SR-A expression and function in primary macrophages via p38 MAPK activation.
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DOI：
10.1186/1471-2172-12-37
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发表时间：
2011-07-07
期刊：
影响因子：
3
通讯作者：
Post SR
中科院分区：
文献类型：
--
作者：
Nikolic D;Calderon L;Du L;Post SR
炎症的特征在于细胞因子（如M-CSF）表达的动态变化以及导致A类清道夫受体（SR-A）配体形成的脂质和蛋白质的修饰。这些变化与巨噬细胞中SR-A表达的改变有关;然而，涉及的细胞内信号通路和SR-A配体调节SR-A表达的程度尚不清楚。为了解决这些问题，SR-A的表达和功能进行了检查，在居民小鼠腹腔巨噬细胞与M-CSF或选择性SR-A配体乙酰化低密度脂蛋白（AcLDL）孵育。M-CSF增加SR-A的表达和功能，并需要p38 MAPK的特异性激活，而不是ERK 1/2或JNK。在去除M-CSF后72小时，增加的SR-A表达和功能恢复到基础水平。我们接下来确定巨噬细胞与SR-A配体的长时间孵育是否改变SR-A表达。相反，大多数受体，这是下调慢性暴露于配体，SR-A的表达是可逆性增加与AcLDL孵育巨噬细胞。AcLDL在野生型巨噬细胞中激活p38，但在SR-A-/-巨噬细胞中不激活，AcLDL诱导的SR-A表达特异性需要p38激活。这些结果表明，在居民巨噬细胞SR-A的表达和功能可以动态调节的巨噬细胞微环境的变化，是典型的炎症过程。特别是，我们的研究结果表明，以前未认识到的作用，配体结合SR-A在上调SR-A的表达和激活p38 MAPK。这样，SR-A可以通过增强巨噬细胞对修饰蛋白质/脂质、细菌和细胞碎片的吸收来调节炎症反应;并通过调节炎症细胞因子、生长因子和蛋白水解酶的产生。
Inflammation is characterized by dynamic changes in the expression of cytokines, such as M-CSF, and modifications of lipids and proteins that result in the formation of ligands for Class A Scavenger Receptors (SR-A). These changes are associated with altered SR-A expression in macrophages; however, the intracellular signal pathways involved and the extent to which SR-A ligands regulate SR-A expression are not well defined. To address these questions, SR-A expression and function were examined in resident mouse peritoneal macrophages incubated with M-CSF or the selective SR-A ligand acetylated-LDL (AcLDL). M-CSF increased SR-A expression and function, and required the specific activation of p38 MAPK, but not ERK1/2 or JNK. Increased SR-A expression and function returned to basal levels 72 hours after removing M-CSF. We next determined whether prolonged incubation of macrophages with SR-A ligand alters SR-A expression. In contrast to most receptors, which are down-regulated by chronic exposure to ligand, SR-A expression was reversibly increased by incubating macrophages with AcLDL. AcLDL activated p38 in wild-type macrophages but not in SR-A-/- macrophages, and p38 activation was specifically required for AcLDL-induced SR-A expression. These results demonstrate that in resident macrophages SR-A expression and function can be dynamically regulated by changes in the macrophage microenvironment that are typical of inflammatory processes. In particular, our results indicate a previously unrecognized role for ligand binding to SR-A in up-regulating SR-A expression and activating p38 MAPK. In this way, SR-A may modulate inflammatory responses by enhancing macrophage uptake of modified protein/lipid, bacteria, and cell debris; and by regulating the production of inflammatory cytokines, growth factors, and proteolytic enzymes.
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DOI：
10.1161/01.atv.14.5.798
发表时间：
1994-05-01
期刊：
ARTERIOSCLEROSIS AND THROMBOSIS
影响因子：
--
作者：
GENG, YJ;KODAMA, T;HANSSON, GK
通讯作者：
HANSSON, GK
影响因子：
4.8
作者：
Jaworowski, A;Wilson, NJ;Hamilton, JA
通讯作者：
Hamilton, JA
DOI：
10.1073/pnas.89.17.8102
发表时间：
1992-09-01
影响因子：
11.1
作者：
MOULTON, KS;WU, H;GLASS, CK
通讯作者：
GLASS, CK
DOI：
10.1084/jem.180.2.705
发表时间：
1994-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
de Villiers WJ;Fraser IP;Hughes DA;Doyle AG;Gordon S
通讯作者：
Gordon S
影响因子：
6.2
作者：
Husemann, J;Loike, JD;Silverstein, SC
通讯作者：
Silverstein, SC