Induction and regulation of IL-15 expression in murine macrophages.

Induction and regulation of IL-15 expression in murine macrophages.
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小鼠巨噬细胞中 IL-15 表达的诱导和调节。

DOI:
10.4049/jimmunol.156.2.735
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发表时间:
1996
影响因子:
4.4
通讯作者:
Alan Sher
Alan Sher
中科院分区:
医学2区
文献类型:
--
作者:
Doherty Tm;R. Seder;Alan Sher

文献摘要

被引文献

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IL-15是最近描述的细胞因子,其在生物活性方面类似于IL-2,刺激T细胞和NK细胞增殖和活化以及增强B细胞扩增和Ab产生。与IL-2不同,IL-15不是由淋巴细胞产生的,而是(至少在免疫系统的细胞中)似乎主要由单核细胞/巨噬细胞合成。我们研究了小鼠巨噬细胞中IL-15的诱导(通过半定量逆转录酶-PCR和生物测定),以响应各种不同的巨噬细胞激活刺激,并比较了IL-15产生的调节与IL-12和TNF-α的调节。发现在每个测试的巨噬细胞群体中,IL-15的最佳诱导需要引发(IFN-γ)和触发(LPS、分枝杆菌或弓形虫)刺激。当与相同巨噬细胞的IL-12 mRNA合成相比时,IL-15 mRNA的产生对下调细胞因子IL-14、IL-13和TGF-β的抑制更具抗性。此外,对大多数其他单核因子具有抑制作用的IL-10增加了刺激后发现的IL-15 mRNA水平。这些数据确定IL-15是巨噬细胞/单核细胞谱系的产物,其在活化时上调。因此,IL-15可以在微生物剂引发免疫应答中发挥重要作用。
IL-15 is a recently described cytokine which resembles IL-2 in its biologic activities, stimulating T cell and NK cell proliferation and activation as well as enhancing B cell expansion and Ab production. Unlike IL-2, IL-15 is not produced by lymphocytes, but instead (at least among cells of the immune system) appears to be synthesized primarily by monocyte/macrophages. We have examined the induction of IL-15 in murine macrophages (by semiquantitative reverse transcriptase-PCR and bioassay) in response to a variety of different macrophage-activating stimuli and compared the regulation of IL-15 production to that of IL-12 and TNF-alpha. Optimal induction of IL-15, in each of the macrophages populations tested, was found to require both priming (IFN-gamma) and triggering (LPS, mycobacteria, or Toxoplasma gondii) stimuli. When compared with IL-12 mRNA synthesis by the same macrophages, IL-15.mRNA production was more resistant to inhibition by the down-regulatory cytokines IL-14, IL-13, and TGF-beta. Moreover, IL-10, which is inhibitory for most other monokines, increased levels of IL-15 mRNA found after stimulation. These data establish IL-15 as a product of the macrophage/monocyte lineage, which is up-regulated on activation. IL-15 could thus play an important role in the initiation of immune responses by microbial agents.