Activation of PI3K/Akt signaling has a dominant negative effect on IL-12 production by macrophages infected with Leishmania amazonensis promastigotes.
Activation of PI3K/Akt signaling has a dominant negative effect on IL-12 production by macrophages infected with Leishmania amazonensis promastigotes.
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PI3K/AKT信号的激活对感染了亚马逊疫苗的巨噬细胞对IL-12的产生具有显着的负面影响。
DOI：
10.1016/j.exppara.2008.12.010
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发表时间：
2009-05
影响因子：
2.1
通讯作者：
Kima, Peter E.
中科院分区：
文献类型：
--
作者：
Ruhland, Aaron;Kima, Peter E.
关键词：
利什曼原虫感染巨噬细胞不会导致IL-12的产生。此外，利什曼原虫感染抑制IL-12的其他有效激活剂引起的IL-12产生。我们提供的证据表明，参与磷脂酰肌醇-3激酶（PI 3 K）信号在亚马逊利什曼原虫感染导致预防IL-12 p70的生产在其p40亚基在骨髓衍生的巨噬细胞（BMDM）的转录水平。用PI 3 K或下游激酶Akt的特异性抑制剂抑制PI 3 K信号传导，逆转IL-12阻断。虽然MAP激酶ERK（p44和p42）在感染L.在亚马逊河中，用PD 98059抑制MEK（ERK上游的激酶）没有逆转IL-12的阻断。此外，抑制其他MAP激酶JNK和p38以及用阻断G蛋白介导的信号传导的百日咳毒素处理细胞，没有逆转利什曼原虫感染对IL-12产生的预防。有趣的是，PI 3 K/Akt信号传导的激活对ERK和p38激活具有不同的影响。综上所述，我们认为利什曼原虫前鞭毛体感染BMDM原虫激活了控制IL-12产生的正信号通路和负信号通路。由感染激活的PI 3 K信号传导是阻止IL-12产生的负信号传导途径。
Infection of macrophages with Leishmania parasites does not result in the production of IL-12. In addition, infection with Leishmania suppresses IL-12 production elicited by otherwise potent activators of IL-12. We provide evidence that engagement of phosphatidyl inositol-3 kinase (PI3K) signaling during Leishmania amazonensis infection leads to the prevention of IL-12 p70 production at the level of transcription of its p40 subunit in bone marrow derived macrophages (BMDMϕ). Inhibition of PI3K signaling with specific inhibitors of PI3K or the downstream kinase Akt, reverses the IL-12 blockade. Although the MAP kinase ERK (p44 and p42) was transiently activated by infection with L. amazonensis, inhibition of MEK, the kinase upstream of ERK, with PD98059, did not reverse the blockade of IL-12. Furthermore, inhibition of the other MAP kinases JNK and p38 as well as treatment of cells with pertussis toxin that blocks G protein mediated signaling, did not reverse the prevention of IL-12 production by Leishmania infection. Interestingly, activation of PI3K/Akt signaling had differential effects on ERK and p38 activation. Taken together we propose that infection of BMDMϕ with Leishmania promastigotes activates both positive and negative signaling pathways that control IL-12 production. PI3K signaling activated by the infection is the negative signaling pathway that prevents IL-12 production.
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影响因子：
15.3
作者：
D'Andrea, A;Aste-Amezaga, M;Valiante, N M;Ma, X;Kubin, M;Trinchieri, G
通讯作者：
Trinchieri, G
影响因子：
30.5
作者：
Fukao, T;Tanabe, M;Koyasu, S
通讯作者：
Koyasu, S
影响因子：
4.4
作者：
Martin, M;Schifferle, RE;Michalek, SM
通讯作者：
Michalek, SM
影响因子：
16.8
作者：
Fukao, T;Koyasu, S
通讯作者：
Koyasu, S
影响因子：
4.4
作者：
Constant, SL;Dong, C;Flavell, RA
通讯作者：
Flavell, RA