Feng W, Wang Y, Zhang J, Wang X, Li C, Chang Z
Shanghai Institute of Cell Biology, Chinese Academy of Sciences, Shanghai, 200031, People's Republic of China.
Biochem Biophys Res Commun. 2000 Mar 16;269(2):570-3. doi: 10.1006/bbrc.2000.2341.
LPS, an endotoxin isolated from gram-negative bacterial, has been shown to be a potent cytokine initiator in murine peritoneal macrophages. CAMP-dependent pathway is generally considered to play a suppressive role in immune response. This study investigated the effect of cAMP on LPS-induced gene expression of cytokines in murine macrophages. Our data clearly demonstrated that in LPS-treated macrophages, cAMP elevator (CTx and 8-bromo-cAMP) could increase IL-1Ra and IL-10 gene expression, while mRNAs of IL-1alpha, IL-12, IL-6, and MIF were decreased and other cytokines like IL-1beta, and IFN-gamma did not give a definite tendency. This is the first report that CTx and 8-bromo-cAMP positively regulate IL-1Ra gene expression in LPS-stimulated macrophages. Our data also suggest that a cAMP-dependent pathway may play a regulatory role in Toll-receptor system.
脂多糖(LPS)是一种从革兰氏阴性菌中分离出的内毒素,已被证明是小鼠腹腔巨噬细胞中一种强大的细胞因子启动剂。环磷酸腺苷(cAMP)依赖性途径通常被认为在免疫反应中起抑制作用。本研究调查了cAMP对LPS诱导的小鼠巨噬细胞中细胞因子基因表达的影响。我们的数据清楚地表明,在经LPS处理的巨噬细胞中,cAMP增强剂(霍乱毒素和8-溴-cAMP)可增加白细胞介素-1受体拮抗剂(IL-1Ra)和白细胞介素-10(IL-10)的基因表达,而白细胞介素-1α(IL-1α)、白细胞介素-12(IL-12)、白细胞介素-6(IL-6)和巨噬细胞移动抑制因子(MIF)的信使核糖核酸(mRNA)水平降低,而其他细胞因子如白细胞介素-1β(IL-1β)和干扰素-γ(IFN-γ)则没有明确的变化趋势。这是关于霍乱毒素和8-溴-cAMP在LPS刺激的巨噬细胞中正向调节IL-1Ra基因表达的首次报道。我们的数据还表明,cAMP依赖性途径可能在Toll受体系统中发挥调节作用。