IFNβ autocrine feedback is required to sustain TLR induced production of MCP-1 in macrophages.
IFNβ autocrine feedback is required to sustain TLR induced production of MCP-1 in macrophages.
复制标题
DOI：
10.1016/j.febslet.2013.03.025
复制
发表时间：
2013-05-21
期刊：
影响因子：
3.5
通讯作者：
Arthur JS
中科院分区：
文献类型：
--
作者：
Pattison MJ;MacKenzie KF;Elcombe SE;Arthur JS
TLR激活可诱导巨噬细胞MCP-1 mRNA水平和蛋白分泌。在LPS的作用下，MCP-1 mRNA的初始诱导不依赖于IFNβ。LPS持续产生MCP-1需要IFNβ介导的反馈回路。poly IC持续产生MCP-1也需要IFNβ。趋化因子，包括MCP-1，由于其招募其他免疫细胞的能力，对建立有效的免疫反应至关重要。我们发现持续的LPS或多（I:C）刺激的MCP-1的产生需要ifn β介导的反馈回路。与此一致的是，外源性IFNβ能够在没有其他刺激的情况下诱导MCP-1转录。用Ruxolitinib（一种JAK抑制剂）阻断IFNβ信号传导可以抑制MCP-1的转录。MCP-1启动子包含潜在的STAT结合位点，我们证明STAT1在IFNβ刺激下被募集。此外，我们发现IL-10敲除会增加MCP-1的产生，以响应LPS，这可能反映了IL-10抑制IFNβ产生的能力。总之，这些结果表明IFNβ和IL-10之间的平衡在MCP-1调控中的重要性。
MCP-1 mRNA levels and protein secretion in macrophages are induced by TLR activation. In response to LPS, the initial induction of MCP-1 mRNA is IFNβ independent. The sustained production of MCP-1 by LPS requires an IFNβ mediated feedback loop. The sustained production of MCP-1 by poly IC also requires IFNβ. Chemokines, including MCP-1, are crucial to mounting an effective immune response due to their ability to recruit other immune cells. We show that sustained LPS or poly(I:C)-stimulated MCP-1 production requires an IFNβ-mediated feedback loop. Consistent with this, exogenous IFNβ was able to induce MCP-1 transcription in the absence of other stimuli. Blocking IFNβ signaling with Ruxolitinib, a JAK inhibitor, inhibited MCP-1 transcription. The MCP-1 promoter contains potential STAT binding sites and we demonstrate that STAT1 is recruited upon IFNβ stimulation. Furthermore we find that IL-10 knockout increases MCP-1 production in response to LPS, which may reflect an ability of IL-10 to repress IFNβ production. Overall, these results show the importance of the balance between IFNβ and IL-10 in the regulation of MCP-1.
登录
查看更多内容
影响因子：
4.6
作者：
Konishi, Hideyuki;Okamoto, Koichi;Ohmori, Yusuke;Yoshino, Hitoshi;Ohmori, Hiroshi;Ashihara, Motooki;Hirata, Yuichi;Ohta, Atsunori;Sakamoto, Hiroshi;Hada, Natsuko;Katsume, Asao;Kohara, Michinori;Morikawa, Kazumi;Tsukuda, Takuo;Shimma, Nobuo;Foster, Graham R.;Alazawi, William;Aoki, Yuko;Arisawa, Mikio;Sudoh, Masayuki
通讯作者：
Sudoh, Masayuki
I型Interferon自分泌 - 核酸环与树突状细胞的Toll样受体诱导的白介素-12p70分泌有关。
影响因子：
15.3
作者：
Gautier, G;Humbert, M;Deauvieau, F;Scuiller, M;Hiscott, J;Bates, EEM;Trinchieri, G;Caux, C;Garrone, P
通讯作者：
Garrone, P
DOI：
10.1084/jem.20050126
发表时间：
2005-12-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Flores-Villanueva PO;Ruiz-Morales JA;Song CH;Flores LM;Jo EK;Montaño M;Barnes PF;Selman M;Granados J
通讯作者：
Granados J
影响因子：
4.4
作者：
Jaramillo, M;Olivier, M
通讯作者：
Olivier, M
影响因子：
2.9
作者：
Handel, TM;Domaille, PJ
通讯作者：
Domaille, PJ