Role of phosphatidylinositol-3-kinase-gamma (PI3Kgamma)-mediated pathway in 17beta-estradiol-induced killing of L. mexicana in macrophages from C57BL/6 mice.
Role of phosphatidylinositol-3-kinase-gamma (PI3Kgamma)-mediated pathway in 17beta-estradiol-induced killing of L. mexicana in macrophages from C57BL/6 mice.
复制标题
磷脂酰肌醇-3-激酶-γ (PI3Kgamma) 介导的途径在 17β-雌二醇诱导的 C57BL/6 小鼠巨噬细胞中墨西哥乳杆菌的杀伤中的作用。
DOI：
10.1038/icb.2008.39
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发表时间：
2008
影响因子：
4
通讯作者：
Satoskar,AbhayR
中科院分区：
文献类型：
--
作者：
Lezama-Dávila,ClaudioM;Isaac-Márquez,AngelicaP;Barbi,Joseph;Cummings,HannahE;Lu,Bao;Satoskar,AbhayR
We recently demonstrated that 17β‐estradiol (E2) enhances killing ofLeishmania mexicanain macrophages from both male and female DBA/2 mouse by increasing nitric oxide (NO) production. Here, we analyzed the effect of E2on leishmanicidal activity and cytokine production by bone marrow‐derived macrophages (BMDMs) from male and female C57BL/6 micein vitro, specifically examining the role of phosphatidylinositol‐3‐kinase‐γ (PI3Kγ) in E2‐induced parasite killing. Unlike its effect on macrophages from both male and female DBA/2 mice, E2only increased leishmanicidal activity in macrophages from female C57BL/6 mice, which was evident by a significant reduction in both infection rates and infection levels compared to sham controls. E2‐treated BMDMs from female C57BL/6 mice expressed higher levels of interferon‐γRα, and also produced more interleukin (IL)‐12, IL‐6 and NO than both the sham controls and E2‐treated male‐derived macrophages. Sham‐treated BMDMs from female PI3Kγ−/−C57BL/6 mice displayed lower infection rates and infection levels compared to sham‐treated wild‐type (WT) macrophages. However E2, unlike its effect on macrophages from female WT C57BL/6 mice, failed to reduce infection rates and infection levels in BMDMs from female PI3Kγ−/−mice. Interestingly, E2‐treated BMDMs from female C57BL/6 mice produced significant amounts of inflammatory cytokines and NO in levels comparable to those observed in sham‐treated PI3Kγ‐deficient macrophages as well as E2‐treated macrophages from WT mice. These findings show that E2exerts a distinct effect on leishmanicidal activity of macrophages from male versus female C57BL/6 mice. In addition, they suggest that PI3Kγ is not required for E2‐induced cytokine and NO production inL. mexicana‐infected macrophages from female C57BL/6 mice but it may be involved in parasite clearance from these cells.
