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首页> 外文期刊>Cytokine >RECOMBINANT TNF-alpha MEDIATED REGULATION OF THE IkappaB-alpha/NF-kappaB SIGNALING PATHWAY: EVIDENCE FOR THE ENHANCEMENT OF PRO- AND ANTI-INFLAMMATORY CYTOKINES IN ALVEOLAR EPITHELIAL CELLS.
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RECOMBINANT TNF-alpha MEDIATED REGULATION OF THE IkappaB-alpha/NF-kappaB SIGNALING PATHWAY: EVIDENCE FOR THE ENHANCEMENT OF PRO- AND ANTI-INFLAMMATORY CYTOKINES IN ALVEOLAR EPITHELIAL CELLS.

机译:重组TNF-α介导的IkappaB-α/ NF-kappaB信号通路的调节:增强小泡上皮细胞促炎和抗炎细胞因子的证据。

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摘要

The signaling transduction mechanism mediated by tumor necrosis factor-alpha (TNF-alpha) in the alveolar epithelium is not well characterized. It was subsequently hypothesized that recombinant murine TNF-alpha (rmTNF-alpha) selectively regulates the inhibitory kappaB (IkappaB-alpha)uclear factor-kappaB (NF-kappaB) pathway and interferes with the endogenous biosynthesis of pro-inflammatory (stimulatory) and anti-inflammatory (inhibitory) cytokines. The cytokine rmTNF-alpha induced, in a time- and dose-dependent manner, the degradation of IkappaB-alpha within the cytosolic compartment, an effect associated with up-regulating its phosphorylation. This allowed the biphasic regulation of selective NF-kappaB subunit nuclear translocation, thereby mediating a dual excitatory mechanism on NF-kappaB activation. The immunoregulatory effect of rmTNF-alpha was associated with a time-dependent induction of pro-inflammatory [interleukin (IL)-1beta, IL-6 and TNF-alpha] and anti-inflammatory (IL-10) cytokine biosynthesis. These results indicate a novel involvement of an IkappaB-alpha/NF-kappaB-sensitive pathway mediating the effect of TNF-alpha, which is associated with an autocrine, endogenous mechanism mediating the regulation of cytokine signaling.
机译:肺泡上皮细胞中的肿瘤坏死因子-α(TNF-alpha)介导的信号转导机制尚不十分清楚。随后假设重组鼠TNF-α(rmTNF-alpha)选择性调节抑制性kappaB(IkappaB-alpha)/核因子-kappaB(NF-kappaB)途径,并干扰促炎性和刺激性的内源性生物合成。抗炎(抑制)细胞因子。细胞因子rmTNF-α以时间和剂量依赖性方式诱导了胞浆区IkappaB-α的降解,这与上调其磷酸化有关。这允许选择性调节NF-κB亚基核易位的双相调节,从而介导NF-κB活化的双重兴奋机制。 rmTNF-α的免疫调节作用与促炎性[白介素(IL)-1β,IL-6和TNF-α的时间依赖性诱导以及抗炎性(IL-10)细胞因子的生物合成有关。这些结果表明,介导TNF-α效应的IkappaB-α/ NF-kappaB敏感途径的新型参与,这与介导细胞因子信号传导调节的自分泌内源性机制有关。

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