Woo Moon-Sook, Jung Soo-Hyun, Hyun Jin-Won, Kim Hee-Sun
Department of Neuroscience, Ewha Institute of Neuroscience, College of Medicine, Ewha Womans University, 70 Jongno 6-Ga, Jongno-Gu, Seoul 110-783, South Korea.
Neurosci Lett. 2004 Feb 19;356(3):187-90. doi: 10.1016/j.neulet.2003.11.056.
This study shows that two cAMP elevating agents, dibutyryl-cAMP (dbcAMP) and forskolin, regulate the expression of several cytokines and inducible nitric oxide synthase (iNOS) in a different manner. Both dbcAMP and forskolin repressed lipopolysaccharide (LPS)-induced TNF-alpha expression and enhanced anti-inflammatory cytokine IL-10 level in the BV2 microglia. In contrast, they differentially regulated the iNOS, IL-6 and IL-1beta expression levels. DbcAMP increased the IL-1beta level without affecting either the IL-6 or iNOS expression, whereas forskolin repressed the IL-6 and iNOS expression level without affecting IL-1beta in the LPS-stimulated microglia. Treatment with H89, a specific inhibitor of protein kinase A (PKA), revealed that an enhancement in the IL-10 and IL-1beta levels by dbcAMP or forskolin totally depends on the PKA pathway, while changes in the other cytokines and iNOS are independent or only partially dependent on the PKA pathway. These results suggest the diverse regulation of the inflammatory reactions depending on different cAMP elevating agents.
本研究表明，两种环磷酸腺苷（cAMP）升高剂，二丁酰环磷腺苷（dbcAMP）和福斯高林，以不同方式调节多种细胞因子和诱导型一氧化氮合酶（iNOS）的表达。dbcAMP和福斯高林均抑制脂多糖（LPS）诱导的BV2小胶质细胞中肿瘤坏死因子-α（TNF-α）的表达，并提高抗炎细胞因子白细胞介素-10（IL-10）的水平。相反，它们对iNOS、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）的表达水平有不同的调节作用。dbcAMP增加IL-1β水平，而不影响IL-6或iNOS的表达，而福斯高林在LPS刺激的小胶质细胞中抑制IL-6和iNOS的表达水平，而不影响IL-1β。用蛋白激酶A（PKA）的特异性抑制剂H89处理后发现，dbcAMP或福斯高林对IL-10和IL-1β水平的提高完全依赖于PKA途径，而其他细胞因子和iNOS的变化则独立或仅部分依赖于PKA途径。这些结果表明，不同的cAMP升高剂对炎症反应有不同的调节作用。
