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Cytokine effects on cell survival and death of A549 lung carcinoma cells

机译:细胞因子对A549肺癌细胞存活和死亡的影响

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Purpose: IL-13, TNF-?? and IL-1?? have various effects on lung cancer growth and death, but the signaling pathways mediating these effects have not been extensively analyzed. Therefore, the effects of IL-13, TNF-?? and IL-1?? alone, and in combination with Fas, on cell viability and death as well as major signaling pathways involved in these effects were investigated in A549 lung carcinoma cells. Results: Using MTT and flow cytometry, IL-13, TNF-?? and IL-1?? pretreatment decreased Fas-induced cell death. These anti-cell death effects were attenuated by pretreatment with inhibitors of Nuclear factor-??B [NF-??B], Phoshatidylinositole-3 kinase [PI3-K], JNK, p38 and ERK1/2 pathways. Using Western blot, IL-13, TNF-?? and IL-1?? treated cells showed time-dependent expression of p-ERK1/2, p-p38, p-JNK, p-Akt and p-I??B?? proteins, decreased I??B?? protein expression, no cleavage of Caspase-3 and PARP1 proteins and no notable alterations of Fas protein. IL-13 and TNF-?? treated cells showed time-dependent increase of FLIPL expression. Conclusion: IL-13, TNF-?? and IL-1?? attenuate the pro-cell death effects of Fas on A549 cells, at least partially, by pathways involving the NF-??B, PI3-K and MAP kinases, but not by alterations of Fas protein expression. The IL-13 and TNF-?? cell survival effects may also be due to increased expression of FLIPL protein. ? 2013 Elsevier Ltd.
机译:目的:IL-13,TNF-α?和IL-1?对肺癌的生长和死亡有多种作用,但尚未广泛分析介导这些作用的信号传导途径。因此,IL-13,TNF-α的作用。和IL-1?在A549肺癌细胞中研究了单独使用或与Fas联合使用对细胞活力和死亡以及参与这些作用的主要信号通路。结果:使用MTT和流式细胞仪检测IL-13,TNF-α和IL-1?预处理可减少Fas诱导的细胞死亡。通过用核因子-βB[NF-βB],磷脂酰肌醇-3激酶[PI3-K],JNK,p38和ERK1 / 2途径的抑制剂预处理减弱了这些抗细胞死亡的作用。使用蛋白质印迹法,IL-13,TNF-α和IL-1?经处理的细胞显示出p-ERK1 / 2,p-p38,p-JNK,p-Akt和p-IαB14的时间依赖性表达。蛋白质,降低了I ?? B ??蛋白表达,Caspase-3和PARP1蛋白均无裂解,Fas蛋白无明显变化。 IL-13和TNF-α处理的细胞显示出FLIPL表达的时间依赖性增加。结论:IL-13,TNF-α?和IL-1?通过涉及NF-κB,PI3-K和MAP激酶的途径,至少部分地减轻Fas对A549细胞的前细胞死亡作用,但不通过改变Fas蛋白表达来减轻。 IL-13和TNF-α细胞存活效应也可能是由于FLIPL蛋白表达增加所致。 ? 2013爱思唯尔有限公司

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