Corsini Emanuela, Di Paola Rosanna, Viviani Barbara, Genovese Tiziana, Mazzon Emanuela, Lucchi Laura, Marinovich Marina, Galli Corrado Lodovico, Cuzzocrea Salvatore
Department of Pharmacological Sciences, University of Milan, Milan, Italy.
Immunology. 2005 Jun;115(2):253-61. doi: 10.1111/j.1365-2567.2005.02148.x.
Ageing is associated with increased susceptibility to lung infections and delayed resolution of pulmonary infiltrates. The purpose of this study was to investigate the effect of age on the onset of carrageenan-induced lung inflammation. When compared with carrageenan-treated young rats (3 months old), old rats (>18 months old) exhibited a preponderance of pleural exudation and polymorphonuclear cell infiltration. Lung myeloperoxidase activity, an index of neutrophil infiltration and activation, was significantly increased in old rats in comparison with young rats. Consistent with the biochemical markers of inflammation, increased lung damage, as assessed by nitrosative stress and lipid peroxidation, was observed in carrageenan-treated old rats. In the lung exudate obtained from old rats, a significant reduction in interleukin-10 (IL-10) was observed, while similar expression of monocyte chemotactic protein-1 was induced, suggesting that a decrease in IL-10 rather than increased chemotaxis may account for the preponderance of the inflammatory cellular infiltrate in old rats. Similar to the in vivo situation, freshly isolated alveolar macrophages obtained from old rats produced less IL-10. This defective IL-10 production could be explained by a reduction in the cAMP-dependent signalling pathway, which mediates IL-10 production. Indeed, we found decreased cAMP-responsive element binding protein (CREB) and phosphorous-CREB (P-CREB) expression in old rats, which may account for reduced IL-10 production in old rats.
衰老与肺部感染易感性增加以及肺部浸润消散延迟有关。本研究的目的是调查年龄对卡拉胶诱导的肺部炎症发病的影响。与卡拉胶处理的年轻大鼠(3个月大)相比,老年大鼠(>18个月大)表现出更多的胸腔渗出和多形核细胞浸润。与年轻大鼠相比,老年大鼠的肺髓过氧化物酶活性(中性粒细胞浸润和活化的指标)显著增加。与炎症的生化标志物一致,在卡拉胶处理的老年大鼠中观察到肺损伤增加,通过亚硝化应激和脂质过氧化评估。在从老年大鼠获得的肺渗出液中,观察到白细胞介素-10(IL-10)显著减少,而单核细胞趋化蛋白-1的表达相似,这表明IL-10的减少而非趋化性增加可能是老年大鼠炎症细胞浸润占优势的原因。与体内情况类似,从老年大鼠新鲜分离的肺泡巨噬细胞产生的IL-10较少。这种IL-10产生缺陷可以通过介导IL-10产生的cAMP依赖性信号通路的减少来解释。事实上,我们发现老年大鼠中cAMP反应元件结合蛋白(CREB)和磷酸化-CREB(P-CREB)表达降低,这可能解释了老年大鼠中IL-10产生减少的原因。