Novel regulation of CCL2 gene expression by murine LITAF and STAT6B.
Novel regulation of CCL2 gene expression by murine LITAF and STAT6B.
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DOI：
10.1371/journal.pone.0025083
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Amar S
中科院分区：
文献类型：
--
作者：
Tang X;Yang Y;Amar S
炎症是一个多方面的过程：作为一种防御机制是有益的，但根据其严重程度和持续时间也是有害的。在损伤部位，炎症细胞被介体级联激活，其中之一是LITAF，一种已知上调TNF-α的转录调节因子。我们先前表明，人LITAF与人STAT 6 B形成复合物，其易位到细胞核中以上调细胞因子转录。为了剖析该复合物的分子意义，开发了鼠模型，并分析了小鼠STAT 6 B（mSTAT 6 B）和小鼠LITAF（mLITAF）之间的相互作用。mLITAF和mSTAT 6 B的表达均依赖于MyD 88和TLR配体。此外，发现mLITAF介导LPS诱导的CCL 2基因转录，并与mSTAT 6 B协同导致CCL 2蛋白表达。在LITAF缺陷小鼠中，与野生型对照动物相比，巨噬细胞中mLITAF介导的CCL 2产生显著减少。通过尾静脉注射6 BsiRNA 1敲低mSTAT 6 B的小鼠导致血清TNF-α和CCL 2产生减少。mLITAF/mSTAT 6 B复合物被认为在LPS诱导的CCL 2表达和可能的其他细胞因子中起作用。
Inflammation is a multifaceted process: beneficial as a defense mechanism but also detrimental depending on its severity and duration. At the site of injury, inflammatory cells are activated by a cascade of mediators, one of which is LITAF, a transcription regulator known to upregulate TNF-α. We previously showed that human LITAF forms a complex with human STAT6B, which translocates into the nucleus to upregulate cytokine transcription. To dissect the molecular implications of this complex, a murine model was developed and interactions between mouse STAT6B (mSTAT6B) and mouse LITAF (mLITAF) were analyzed. Both mLITAF and mSTAT6B expression were MyD88- and TLR ligand-dependent. Furthermore, mLITAF was found to mediate LPS-induced CCL2 gene transcription with the cooperation of mSTAT6B leading to CCL2 protein expression. In LITAF-deficient mice, mLITAF-mediated CCL2 production in macrophages was significantly reduced compared to the wild-type control animals. Mice knockdown for mSTAT6B by 6BsiRNA1 tail vein injection resulted in a decrease in serum TNF-α and CCL2 production. mLITAF/mSTAT6B complex is proposed to play a role in LPS-induced CCL2 expression and possibly other cytokines.
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影响因子：
9.8
作者：
Church DM;Goodstadt L;Hillier LW;Zody MC;Goldstein S;She X;Bult CJ;Agarwala R;Cherry JL;DiCuccio M;Hlavina W;Kapustin Y;Meric P;Maglott D;Birtle Z;Marques AC;Graves T;Zhou S;Teague B;Potamousis K;Churas C;Place M;Herschleb J;Runnheim R;Forrest D;Amos-Landgraf J;Schwartz DC;Cheng Z;Lindblad-Toh K;Eichler EE;Ponting CP;Mouse Genome Sequencing Consortium
通讯作者：
Mouse Genome Sequencing Consortium
DOI：
10.1073/pnas.0630562100
发表时间：
2003-04-01
影响因子：
11.1
作者：
Tang, XR;Fenton, MJ;Amar, S
通讯作者：
Amar, S
DOI：
10.1073/pnas.96.8.4518
发表时间：
1999-04-13
影响因子：
11.1
作者：
Myokai, F;Takashiba, S;Amar, S
通讯作者：
Amar, S
影响因子：
14.2
作者：
Peters, Marcus;Kauth, Marion;Bufe, Albrecht
通讯作者：
Bufe, Albrecht
影响因子：
--
作者：
Klein, Rachel;Rosenbach, Misha;Dunham, Jonathan
通讯作者：
Dunham, Jonathan