Gly80Ser Polymorphism of Phospholipase A2-IID Is Associated with Cytokine Inducibility in A549 Cells
Gly80Ser Polymorphism of Phospholipase A2-IID Is Associated with Cytokine Inducibility in A549 Cells
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DOI：
10.1159/000213243
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发表时间：
2009-01-01
期刊：
影响因子：
3.7
通讯作者：
Kubota, Isao
中科院分区：
文献类型：
--
作者：
Igarashi, Akira;Shibata, Yoko;Kubota, Isao
背景资料：磷脂酶A2-IID（PLA 2G 2D，NCBI SNP参考：rs 584367）中的Gly 80 Ser多态性与慢性阻塞性肺疾病（COPD）患者的体重减轻相关。T等位基因错义突变导致PLA 2G 2D蛋白的第80个氨基酸从甘氨酸（Gly; C等位基因）变为丝氨酸（Ser; T等位基因）。与携带Gly的患者相比，携带Ser的COPD患者体重明显减轻。携带该Ser等位基因后体重减轻的机制尚未阐明。目的：我们的目的是评估这种等位基因的变化是否改变PLA 2酶活性和/或促炎细胞因子诱导。研究方法：用PLA_2 G_2 D-Gly和PLA_2 G_2 D-Ser转染人肺上皮细胞株A549，检测细胞内PLA_2活性和细胞因子表达。结果：A549-PLA 2G 2D-Ser细胞和A549-PLA 2G 2D-Gly细胞sPLA 2酶活性无明显差异。A549-PLA 2G 2D-Ser细胞比A549-PLA 2G 2D-Gly细胞自发产生更高水平的白细胞介素（IL）-6和IL-8。在肿瘤坏死因子-α刺激下，A549-PLA 2G 2D-Ser细胞中IL-6和IL-8的mRNA和蛋白水平与A549-PLA 2G 2D-Gly细胞相比升高。在过氧化氢刺激下，A549-PLA 2G 2D-Ser细胞中IL-8 mRNA和蛋白水平高于A549-PLA 2G 2D-Gly细胞。结论：PLA 2G 2D-Ser较PLA 2G 2D-Gly能增强IL-6和IL-8的表达。在PLA 2G 2D等位基因改变的情况下观察到的这种增强的细胞因子表达可能与COPD患者中观察到的体重减轻相关。版权所有（C）2009 S. Karger AG，巴塞尔
Background: The Gly80Ser polymorphism in phospholipase A2-IID (PLA2G2D, NCBI SNP reference: rs584367) is associated with a loss in body weight in patients with chronic obstructive pulmonary disease (COPD). The T allele missense mutation results in the 80th amino acid of the PLA2G2D protein changing from a glycine (Gly; C allele) to a serine (Ser; T allele). COPD patients carrying Ser lose a significant amount of weight compared with those carrying Gly. The mechanism for this weight loss following carriage of this Ser allele has not been clarified. Objectives: We aimed to evaluate whether this allelic change alters PLA2 enzymatic activity and/or pro-inflammatory cytokine inducibility. Methods: A549 cells (a human pulmonary epithelial cell line) were transfected with PLA2G2D-Gly or PLA2G2D-Ser. We evaluated PLA2 activity and cytokine expressions in these cells. Results: The enzymatic activity of sPLA2 in A549-PLA2G2D-Ser cells did not differ from the A549-PLA2G2D-Gly cells. A549-PLA2G2D-Ser cells spontaneously produced higher levels of interleukin (IL)-6 and IL-8 than A549-PLA2G2D-Gly cells. Upon tumor necrosis factor-alpha stimulation, IL-6 and IL-8 mRNA and protein levels in A549-PLA2G2D-Ser cells were elevated compared with those of A549-PLA2G2D-Gly cells. Upon hydrogen peroxide stimulation, IL-8 mRNA and protein levels in A549-PLA2G2D-Ser cells were higher than those of A549-PLA2G2D-Gly cells. Conclusions: PLA2G2D-Ser enhances the expression of IL-6 and IL-8 compared with PLA2G2D-Gly. This enhanced cytokine expression observed with the allelic change in PLA2G2D may be associated with the body weight loss seen in COPD patients. Copyright (C) 2009 S. Karger AG, Basel