Adenosine 5'-monophosphate-activated protein kinase promotes macrophage polarization to an anti-inflammatory functional phenotype.
Adenosine 5'-monophosphate-activated protein kinase promotes macrophage polarization to an anti-inflammatory functional phenotype.
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DOI：
10.4049/jimmunol.181.12.8633
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发表时间：
2008-12-15
期刊：
影响因子：
--
通讯作者：
Suttles J
中科院分区：
文献类型：
--
作者：
Sag D;Carling D;Stout RD;Suttles J
在此，我们证明了AMP活化蛋白激酶（AMPK）作为巨噬细胞中炎症信号通路的有效反调节剂的作用。用抗炎细胞因子刺激巨噬细胞（即，IL-10和TGFβ）导致AMPK的快速磷酸化/活化，而用促炎刺激物（LPS）刺激巨噬细胞导致AMPK去磷酸化/失活。RNA干扰抑制AMPKα表达可显著增加LPS诱导的TNFα、IL-6和环氧合酶- 2（考克斯-2）的mRNA水平。同样，巨噬细胞中显性负性AMPKα1的表达增强了对LPS刺激的TNFα和IL-6蛋白合成，同时减少了IL-10的产生。相反，用AMPKα1的组成型活性形式转染巨噬细胞导致LPS诱导的TNFα和IL-6产生减少，IL-10产生增加。AMPK对LPS诱导的IκB-α降解有负调节作用，对Akt的激活有正调节作用，并伴有对GSK 3-β的抑制和对CREB的激活。因此，AMPK以抑制促炎反应并促进巨噬细胞极化为抗炎功能表型的方式指导巨噬细胞中的信号传导途径。
Herein, we demonstrate a role of AMP-activated protein kinase (AMPK) as a potent counter-regulator of inflammatory signaling pathways in macrophages. Stimulation of macrophages with anti-inflammatory cytokines (i.e., IL-10 and TGFβ) resulted in the rapid Phosphorylation/activation of AMPK, whereas stimulation of macrophages with a proinflammatory stimulus (LPS) resulted in AMPK dephosphorylation/inactivation. Inhibition of AMPKα expression by RNA interference dramatically increased the mRNA levels of LPS-induced TNFα, IL-6 and cyclooxygenase- 2 (COX-2). Likewise, expression of a dominant negative AMPKα1 in macrophages enhanced TNFα and IL-6 protein synthesis in response to LPS stimulation, while diminishing the production of IL-10. In contrast, transfection of macrophages with a constitutively active form of AMPKα1 resulted in decreased LPS-induced TNFα and IL-6 production, and heightened production of IL-10. In addition, we found that AMPK negatively regulated LPS-induced IκB-α degradation and positively regulated Akt activation, accompanied by inhibition of GSK3-β and activation of CREB. Thus, AMPK directs signaling pathways in macrophages in a manner that suppresses proinflammatory responses and promotes macrophage polarization to an anti-inflammatory functional phenotype.
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影响因子：
--
作者：
Hawley SA;Boudeau J;Reid JL;Mustard KJ;Udd L;Mäkelä TP;Alessi DR;Hardie DG
通讯作者：
Hardie DG
影响因子：
4.4
作者：
Mukundan, L;Bishop, GA;Suttles, J
通讯作者：
Suttles, J
影响因子：
4.4
作者：
Nath, N;Giri, S;Singh, I
通讯作者：
Singh, I
DOI：
10.1016/j.bbrc.2004.04.035
发表时间：
2004-05-28
影响因子：
3.1
作者：
Jhun, BS;Jin, QR;Kang, I
通讯作者：
Kang, I
影响因子：
4.8
作者：
HENIN, N;VINCENT, MF;VANDENBERGHE, G
通讯作者：
VANDENBERGHE, G