Chaves Míriam Martins, Costa Daniela Caldeira, de Oliveira Bárbara Fonseca, Rocha Marcella Israel, Nogueira-Machado José Augusto
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Mech Ageing Dev. 2009 Sep;130(9):588-91. doi: 10.1016/j.mad.2009.07.001. Epub 2009 Jul 15.
There is a large increase in the number of elderly people in modern societies. This demographic phenomenon has been paralleled by an epidemic of chronic diseases and inflammatory processes usually associated with advanced age.
We studied the role of protein kinase A (PKA), protein kinase B (Akt/PKB) and p38 mitogen-activated protein kinase (p38 MAPK) signaling pathways in ROS produced by neutrophils induced by pro-interferon-gamma (IFN-gamma) or anti-inflammatory interleukin 10 (IL-10) cytokines age-related.
The ROS generation was studied in healthy subjects in age ranging from 20 to 80 years old divided in five age groups: (20-39), (40-49), (50-59), (60-69) and (70-80) years old. ROS production was quantified in a luminol-dependent chemiluminescence assay and the results were expressed as relative light units/min).
ROS production in human neutrophil was activated by IFN-gamma in all the groups studied. This activation was down-regulated by IL-10. The inhibitory effect of IL-10 on 20-49 years old group was reversed by the pre-treatment with H89 (PKA inhibitor) but not with PD169316 (p38 MAPK inhibitor). This differential effect of IL-10 associated with age was not observed with the neutrophil pre-treatment with Akt/PKB or NADPH-oxidase inhibitor (DPI). Lack of IL-10 effect on ROS production was observed in older subjects (50-80 years old). The effect of IL-10 showed a significant inhibition of ROS production similar to those got with PD169316 alone as compared to that of p38 MAPK.
The results suggest that inhibitory effect of the ROS production mediated by IL-10 depends on PKA for the younger and the lack effect on the elderly is p38 MAPK dependent.
现代社会中老年人数量大幅增加。这一人口现象伴随着通常与高龄相关的慢性疾病和炎症过程的流行。
我们研究了蛋白激酶A（PKA）、蛋白激酶B（Akt/PKB）和p38丝裂原活化蛋白激酶（p38 MAPK）信号通路在促炎性干扰素-γ（IFN-γ）或抗炎性白细胞介素10（IL-10）细胞因子诱导的中性粒细胞产生的活性氧（ROS）中的作用，这些细胞因子与年龄相关。
在年龄范围为20至80岁的健康受试者中研究ROS的产生，这些受试者分为五个年龄组：（20-39）、（40-49）、（50-59）、（60-69）和（70-80）岁。通过鲁米诺依赖性化学发光测定法对ROS产生进行定量，结果以相对光单位/分钟表示。
在所有研究组中，IFN-γ均可激活人中性粒细胞中的ROS产生。IL-10可下调这种激活作用。用H89（PKA抑制剂）预处理可逆转IL-10对20-49岁组的抑制作用，但用PD169316（p38 MAPK抑制剂）预处理则不能。在用Akt/PKB或NADPH氧化酶抑制剂（DPI）预处理中性粒细胞时，未观察到IL-10与年龄相关的这种差异效应。在老年受试者（50-80岁）中未观察到IL-10对ROS产生的影响。与p38 MAPK相比，IL-10的作用显示出对ROS产生的显著抑制作用，类似于单独使用PD169316时的抑制作用。
结果表明，IL-10介导的ROS产生抑制作用在年轻人中依赖于PKA，而在老年人中缺乏作用则依赖于p38 MAPK。
