Department of Biology, University of Rome "Tor Vergata", Via della Ricerca Scientifica 1, 00133 Rome, Italy.
Peptides. 2013 Dec;50:100-8. doi: 10.1016/j.peptides.2013.09.002. Epub 2013 Oct 11.
Atrial natriuretic peptide (ANP), a cardiovascular hormone, elicits different biological actions in the immune system. The aim of the present study was to investigate in THP-1 monocytes the ANP effect on hydrogen peroxide (H2O2)-induced Reactive Oxygen Species (ROS), cell proliferation and migration. A significant increase of H2O2-dependent ROS production was induced by physiological concentration of ANP (10(-10)M). The ANP action was partially affected by cell pretreatment with PD98059, an inhibitor of mitogen activated-protein kinases (MAPK) as well as by wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K) and totally suppressed by diphenylene iodonium (DPI), an inhibitor of the enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The hormone effect was mimicked by cANF and an ANP/NPR-C signaling pathway was studied using pertussis toxin (PTX). A significant increase of H2O2-induced cell migration was observed after ANP (10(-10)M) treatment, conversely a decrease of THP-1 proliferation, due to cell death, was found. Both ANP actions were partially prevented by DPI. Moreover, H2O2-induced release of IL-9, TNF-α, MIP-1α and MIP-1β was not counteracted by DPI, whereas no effect was observed in any experimental condition for both IL-6 and IL-1β. Our results support the view that ANP can play a key role during the inflammatory process.
心钠肽（ANP），一种心血管激素，在免疫系统中引发不同的生物学作用。本研究旨在探讨 ANP 对 THP-1 单核细胞中过氧化氢（H2O2）诱导的活性氧（ROS）、细胞增殖和迁移的影响。生理浓度的 ANP（10（-10）M）可显著增加 H2O2 依赖性 ROS 的产生。ANP 作用部分受细胞用 PD98059 预处理的影响，PD98059 是丝裂原活化蛋白激酶（MAPK）抑制剂，以及wortmannin，磷脂酰肌醇 3-激酶（PI3K）抑制剂，完全被二苯基碘鎓（DPI）抑制，NADPH 氧化酶的酶抑制剂。激素作用被 cANF 模拟，并且使用百日咳毒素（PTX）研究了 ANP/NPR-C 信号通路。在用 H2O2 处理后，观察到 ANP（10（-10）M）处理后 H2O2 诱导的细胞迁移显著增加，相反，由于细胞死亡，THP-1 增殖减少。DPI 部分预防了 ANP 的这两种作用。此外，DPI 没有抵消 H2O2 诱导的白细胞介素-9（IL-9）、肿瘤坏死因子-α（TNF-α）、巨噬细胞炎性蛋白-1α（MIP-1α）和巨噬细胞炎性蛋白-1β（MIP-1β）的释放，但在任何实验条件下，IL-6 和 IL-1β 均未观察到作用。我们的结果支持 ANP 在炎症过程中可以发挥关键作用的观点。
