Selective induction of the beta chemokine C10 by IL-4 in mouse macrophages.
Selective induction of the beta chemokine C10 by IL-4 in mouse macrophages.
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DOI：
10.4049/jimmunol.152.10.5084
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发表时间：
1994-05
影响因子：
4.4
通讯作者：
A. Orlofsky;E. Lin;M. Prystowsky
中科院分区：
文献类型：
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作者：
A. Orlofsky;E. Lin;M. Prystowsky
β趋化因子是通常由活化的巨噬细胞或淋巴细胞产生的8-至12-kDa白细胞化学引诱物的家族。我们研究了最近描述的，但功能上尚未表征的，鼠β趋化因子，C10的表达在原代巨噬细胞中，并将其调节与其他几种β趋化因子的调节进行了对比。虽然其他三种β趋化因子，巨噬细胞炎性蛋白-1 α（MIP-1 α），JE和RANTES，都是由LPS处理骨髓源性巨噬细胞（BMM）和/或常驻腹膜巨噬细胞（RPM）诱导的，但从未观察到C10的LPS刺激。相反，IL-3和粒细胞巨噬细胞-CSF（GM-CSF）强烈诱导C10在两个巨噬细胞群体，而MIP-1 α和RANTES显示出较弱的诱导局限于BMM。JE被强烈诱导，但仅在BMM中。最后，IL-4在BMM和RPM中以剂量依赖性方式强烈诱导C10，但未能刺激其他三种β趋化因子中的任何一种。C10蛋白在培养上清中的积累与mRNA的诱导有关，IL-4和GM-CSF的联合使用导致蛋白水平的增加。放线菌酮完全阻断了C10细胞因子的表达，而其他三种趋化因子都在这种抑制剂的存在下过表达。这些结果表明，C10表达的调节和其他趋化因子之间的急剧分歧，并建议，这种分子可能有不同的功能，在主机防御。
The beta chemokines are a family of 8- to 12-kDa leukocyte chemoattractants that are typically produced by activated macrophages or lymphocytes. We examined the expression in primary macrophages of a recently described, and as yet functionally uncharacterized, murine beta chemokine, C10, and contrasted its regulation with that of several other beta chemokines. Although three other beta chemokines, macrophage inflammatory protein-1 alpha (MIP-1 alpha), JE, and RANTES, were all induced by LPS treatment of bone marrow-derived macrophages (BMM) and/or resident peritoneal macrophages (RPM), LPS stimulation of C10 was never observed. Conversely, IL-3 and granulocyte macrophage-CSF (GM-CSF) strongly induced C10 in both macrophage populations, whereas MIP-1 alpha and RANTES showed a weaker induction restricted to BMM. JE was strongly induced but only in BMM. Finally, IL-4 strongly induced C10 in a dose-dependent manner in both BMM and RPM but failed to stimulate any of the other three beta chemokines. The accumulation of C10 protein in culture supernatants paralleled the induction of mRNA, and the combination of IL-4 and GM-CSF led to enhanced protein levels. The expression of the C10 message in response to cytokines was completely blocked by cycloheximide, whereas the other three chemokines were all overexpressed in the presence of this inhibitor. These results demonstrate a sharp divergence between the regulation of C10 expression and that of other chemokines and suggest that this molecule may have distinct functions in host defense.