Bacterial DNA induces murine interferon-gamma production by stimulation of interleukin-12 and tumor necrosis factor-alpha
Bacterial DNA induces murine interferon-gamma production by stimulation of interleukin-12 and tumor necrosis factor-alpha
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DOI：
10.1006/cimm.1996.0009
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发表时间：
1996-01-10
影响因子：
4.3
通讯作者：
Pisetsky, DS
中科院分区：
文献类型：
--
作者：
Halpern, MD;Kurlander, RJ;Pisetsky, DS
细菌，而不是哺乳动物的DNA，可以在小鼠脾细胞中诱导干扰素γ (ifn - γ)。为了阐明这种活性的基础，我们评估了C3H/HeJ脾细胞在体外产生的细胞因子，分别用大肠杆菌DNA或含有从DNA中鉴定的活性回文序列的合成寡核苷酸刺激。这两种DNA都诱导ifn - γ产生，对DNA酶消化的敏感性表明需要完整的DNA。对分离的细胞群进行评估，以确定DNA对细胞的直接或间接影响。虽然细菌DNA不能在非贴壁细胞群中诱导ifn - γ，但受DNA刺激的贴壁细胞的上清液诱导这些细胞产生ifn - γ。在ifn - γ之前，在dna刺激的脾细胞上清中可检测到白细胞介素-l2 (IL-12)，并且针对IL-12的中和抗体显著抑制ifn - γ的诱导。抗肿瘤坏死因子- α (tnf - α)抗体也能抑制ifn - γ的产生，抗il -12和抗tnf -a联合使用可完全抑制ifn - γ的产生。综上所述，这些结果表明细菌DNA对ifn - γ产生的刺激是由IL-12和tnf - α介导的，并指出巨噬细胞/单核细胞是这种大分子的作用靶点。(C) 1996学术出版社，Inc.
Bacterial, but not mammalian DNA, can induce interferon-gamma (IFN-gamma) in murine splenocytes. To elucidate the basis of this activity, we have assessed in vitro cytokine production by C3H/HeJ splenocytes stimulated with either DNA from Escherichia coli or a synthetic oligonucleotide containing an active palindromic sequence identified from DNA. Both DNAs induced IFN-gamma production, with the requirement for intact DNA shown by sensitivity to DNase digestion. Fractionated cell populations were evaluated to determine direct or indirect cellular effects of the DNA. Although bacterial DNA failed to induce IFN-gamma in the nonadherent cell population, supernatants from adherent cells stimulated by DNA induced IFN-gamma production by these cells. Interleukin-l2 (IL-12) was detectable in supernatants from DNA-stimulated splenocytes before IFN-gamma, and neutralizing antibodies directed against IL-12 markedly inhibited the induction of IFN-gamma. Anti-tumor necrosis factor-alpha (TNF-alpha) antibodies also inhibited IFN-gamma production, and the combination of both anti-IL-12 and anti-TNF-a could totally inhibit production of IFN-gamma. Taken together, these results indicate that the stimulation of IFN-gamma production by bacterial DNA is mediated by IL-12 and TNF-alpha and point to macrophages/monocytes as targets of action of this macromolecule. (C) 1996 Academic Press, Inc.