Histone deacetylases and NF-kB signaling coordinate expression of CX3CL1 in epithelial cells in response to microbial challenge by suppressing miR-424 and miR-503.
Histone deacetylases and NF-kB signaling coordinate expression of CX3CL1 in epithelial cells in response to microbial challenge by suppressing miR-424 and miR-503.
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DOI：
10.1371/journal.pone.0065153
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chen XM
中科院分区：
文献类型：
--
作者：
Zhou R;Gong AY;Chen D;Miller RE;Eischeid AN;Chen XM
NF-kB 通路是上皮免疫防御的关键，并与抗菌肽的分泌、细胞因子/趋化因子的释放以动员免疫效应细胞以及适应性免疫的激活有关。感染后许多炎症基因的表达涉及染色质结构的重塑。我们在此报道，小隐孢子虫感染后，组蛋白脱乙酰酶 (HDAC) 和 NF-kB 信号协调上皮细胞中 CX3CL1 的表达。在感染后培养的人胆管上皮细胞中检测到 CX3CL1 的上调。 miR-424和miR-503的表达下调，并参与感染细胞中CX3CL1的诱导。小隐孢子虫感染以 NF-kB 和 HDAC 依赖性方式抑制 mir-424-503 基因的转录。在受感染的细胞中观察到 NF-kB p50 和 HDAC 的启动子募集增加，以及与 mir-424-503 基因相关的启动子 H3 乙酰化减少。在体内微小念珠菌感染期间，检测到胆道上皮细胞中 CX3CL1 的上调和 CX3CR1+ 细胞浸润的增加。在上皮细胞中还检测到响应 LPS 刺激的 CX3CL1 诱导以及 miR-424 和 miR-503 的下调。上述结果表明，HDAC 和 NF-kB 信号传导协调 CX3CL1 的上皮表达，通过抑制 mir-424-503 基因来促进粘膜抗菌防御。
The NF-kB pathway is key to epithelial immune defense and has been implicated in secretion of antimicrobial peptides, release of cytokines/chemokines to mobilize immune effector cells, and activation of adaptive immunity. The expression of many inflammatory genes following infection involves the remodeling of the chromatin structure. We reported here that histone deacetylases (HDACs) and NF-kB signaling coordinate expression of CX3CL1 in epithelial cells following Cryptosporidium parvum infection. Upregulation of CX3CL1 was detected in cultured human biliary epithelial cells following infection. Expression of miR-424 and miR-503 was downregulated, and was involved in the induction of CX3CL1 in infected cells. C. parvum infection suppressed transcription of the mir-424-503 gene in a NF-kB- and HDAC-dependent manner. Increased promoter recruitment of NF-kB p50 and HDACs, and decreased promoter H3 acetylation associated with the mir-424-503 gene were observed in infected cells. Upregulation of CX3CL1 in biliary epithelial cells and increased infiltration of CX3CR1+ cells were detected during C. parvum infection in vivo. Induction of CX3CL1 and downregulation of miR-424 and miR-503 were also detected in epithelial cells in response to LPS stimulation. The above results indicate that HDACs and NF-kB signaling coordinate epithelial expression of CX3CL1 to promote mucosal antimicrobial defense through suppression of the mir-424-503 gene.
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影响因子：
20.3
作者：
Roger, Thierry;Lugrin, Jerome;Calandra, Thierry
通讯作者：
Calandra, Thierry
DOI：
10.1073/pnas.0706963104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Rosa, A.;Ballarino, M.;Bozzoni, I.
通讯作者：
Bozzoni, I.
影响因子：
4.8
作者：
Hong, SH;Park, SJ;Cheong, JH
通讯作者：
Cheong, JH
影响因子：
--
作者：
Peserico A;Simone C
通讯作者：
Simone C
DOI：
10.1645/ge-2703.1
发表时间：
2011-10
期刊：
The Journal of parasitology
影响因子：
--
作者：
O'Hara SP;Bogert PS;Trussoni CE;Chen X;LaRusso NF
通讯作者：
LaRusso NF