期刊
JOURNAL OF IMMUNOLOGY
卷 190, 期 9, 页码 4812-4820出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1300089
关键词
-
类别
资金
- Deutsche Forschungsgemeinschaft [SFB685, SFB773, GRK1302]
- Bundesministerium fur Bildung und Forschung (AID-NET)
CCL2, also referred to as MCP-1, is critically involved in directing the migration of blood monocytes to sites of inflammation. Consequently, excessive CCL2 secretion has been linked to many inflammatory diseases, whereas a lack of expression severely impairs immune responsiveness. We demonstrate that I kappa B zeta, an atypical I kappa B family member and transcriptional coactivator required for the selective expression of a subset of NF-kappa B target genes, is a key activator of the Ccl2 gene. I kappa B zeta-deficient macrophages exhibited impaired secretion of CCL2 when challenged with diverse inflammatory stimuli, such as LPS or peptidoglycan. These findings were reflected at the level of Ccl2 gene expression, which was tightly coupled to the presence of I kappa B zeta. Moreover, mechanistic insights acquired by chromatin immunoprecipitation demonstrate that I kappa B zeta is directly recruited to the proximal promoter region of the Ccl2 gene and is required for transcription-enhancing histone H3 at lysine-4 trimethylation. Finally, I kappa B zeta-deficient mice showed significantly impaired CCL2 secretion and monocyte infiltration in an experimental model of peritonitis. Together, these findings suggest a distinguished role of I kappa B zeta in mediating the targeted recruitment of monocytes in response to local inflammatory events. The Journal of Immunology, 2013, 190: 4812-4820.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据