Methylthioadenosine reprograms macrophage activation through adenosine receptor stimulation.
Methylthioadenosine reprograms macrophage activation through adenosine receptor stimulation.
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通过腺苷受体刺激将巨噬细胞激活重新编程。
DOI：
10.1371/journal.pone.0104210
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Salter RD
中科院分区：
文献类型：
--
作者：
Keyel PA;Romero M;Wu W;Kwak DH;Zhu Q;Liu X;Salter RD
调节炎症是必要的，以平衡足够的病原体清除和过度的组织损伤。调节炎症的核心是从促炎途径到抗炎途径的转换。巨噬细胞处于启动这一开关的有利位置，因此是多种疗法的靶点。甲硫腺苷就是这样一种潜在的治疗方法，它可以抑制脂多糖刺激后肿瘤坏死因子α的产生。我们发现甲氨蝶呤可以阻断多个TLR配体产生肿瘤坏死因子α。此外，它还可抑制CD69和CD86的表面表达，并减少核因子-KB信号转导。然后我们确定MTA这种作用的机制是通过腺苷A2受体传递信号。A2受体和TLR受体协同作用促进抗炎表型，因为MTA增强了对脂多糖的耐受性。相反，IL-1β的产生和加工不受MTA暴露的影响。综上所述，这些数据表明MTA通过腺苷受体对TLR激活通路进行重新编程，以促进炎症的消退。
Regulation of inflammation is necessary to balance sufficient pathogen clearance with excessive tissue damage. Central to regulating inflammation is the switch from a pro-inflammatory pathway to an anti-inflammatory pathway. Macrophages are well-positioned to initiate this switch, and as such are the target of multiple therapeutics. One such potential therapeutic is methylthioadenosine (MTA), which inhibits TNFα production following LPS stimulation. We found that MTA could block TNFα production by multiple TLR ligands. Further, it prevented surface expression of CD69 and CD86 and reduced NF-KB signaling. We then determined that the mechanism of this action by MTA is signaling through adenosine A2 receptors. A2 receptors and TLR receptors synergized to promote an anti-inflammatory phenotype, as MTA enhanced LPS tolerance. In contrast, IL-1β production and processing was not affected by MTA exposure. Taken together, these data demonstrate that MTA reprograms TLR activation pathways via adenosine receptors to promote resolution of inflammation.
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影响因子：
7.3
作者：
Ohta A;Kini R;Ohta A;Subramanian M;Madasu M;Sitkovsky M
通讯作者：
Sitkovsky M
影响因子：
13.5
作者：
Ara, Ainhoa Iglesias;Xia, Meng;Lu, Shelly C.
通讯作者：
Lu, Shelly C.
影响因子：
4.2
作者：
Keyel PA;Roth R;Yokoyama WM;Heuser JE;Salter RD
通讯作者：
Salter RD
DOI：
10.1073/pnas.1206701109
发表时间：
2012-08-28
影响因子：
11.1
作者：
Ko, Dennis C.;Gamazon, Eric R.;Miller, Samuel I.
通讯作者：
Miller, Samuel I.
影响因子：
3.7
作者：
Latasa MU;Gil-Puig C;Fernández-Barrena MG;Rodríguez-Ortigosa CM;Banales JM;Urtasun R;Goñi S;Méndez M;Arcelus S;Juanarena N;Recio JA;Lotersztajn S;Prieto J;Berasain C;Corrales FJ;Lecanda J;Avila MA
通讯作者：
Avila MA