Vuletic S, Dong W, Wolfbauer G, Tang C, Albers J J
Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
Biochim Biophys Acta. 2011 Oct;1813(10):1917-24. doi: 10.1016/j.bbamcr.2011.06.013. Epub 2011 Jul 3.
Phospholipid transfer protein (PLTP) plays an important role in regulation of inflammation. Previously published studies have shown that PLTP binds, transfers and neutralizes bacterial lipopolysaccharides. In the current study we tested the hypothesis that PLTP can also regulate anti-inflammatory pathways in macrophages. Incubation of macrophage-like differentiated THP1 cells and human monocyte-derived macrophages with wild-type PLTP in the presence or absence of tumor necrosis factor alpha (TNFα) or interferon gamma (IFNγ) significantly increased nuclear levels of active signal transducer and activator of transcription 3, pSTAT3(Tyr705) (p<0.01). Similar results were obtained in the presence of a PLTP mutant without lipid transfer activity (PLTP(M159E)), suggesting that PLTP-mediated lipid transfer is not required for activation of the STAT3 pathway. Inhibition of ABCA1 by chemical inhibitor, glyburide, as well as ABCA1 RNA inhibition, reversed the observed PLTP-mediated activation of STAT3. In addition, PLTP reduced nuclear levels of active nuclear factor kappa-B (NFκB) p65 and secretion of pro-inflammatory cytokines in conditioned media of differentiated THP1 cells and human monocyte-derived macrophages. Our data suggest that PLTP has anti-inflammatory capabilities in macrophages.
磷脂转运蛋白（PLTP）在炎症调节中发挥重要作用。先前发表的研究表明，PLTP可结合、转运并中和细菌脂多糖。在本研究中，我们检验了PLTP也能调节巨噬细胞抗炎途径的假说。在有或无肿瘤坏死因子α（TNFα）或干扰素γ（IFNγ）存在的情况下，将野生型PLTP与巨噬细胞样分化的THP1细胞及人单核细胞衍生的巨噬细胞共同孵育，显著增加了活性信号转导子和转录激活子3（pSTAT3(Tyr705)）的核水平（p<0.01）。在存在无脂质转运活性的PLTP突变体（PLTP(M159E)）的情况下也获得了类似结果，这表明STAT3途径的激活不需要PLTP介导的脂质转运。用化学抑制剂格列本脲抑制ABCA1以及抑制ABCA1 RNA，可逆转观察到的PLTP介导的STAT3激活。此外，PLTP降低了分化的THP1细胞及人单核细胞衍生的巨噬细胞条件培养基中活性核因子κB（NFκB）p65的核水平及促炎细胞因子的分泌。我们的数据表明，PLTP在巨噬细胞中具有抗炎能力。
