Grimaldi M, Pozzoli G, Navarra P, Preziosi P, Schettini G
Dipartimento di Scienza delle Communicazioni Umane, Facoltà di Medicina e Chirurgia, Università di Napoli Federico II, Italy.
J Neurochem. 1994 Jul;63(1):344-50. doi: 10.1046/j.1471-4159.1994.63010344.x.
In this study we analyzed the involvement of the cyclic AMP (cAMP)-protein kinase A system in the regulation of interleukin 6 production by cultured cortical astrocytes. Vasoactive intestinal peptide strongly increased, in a dose-dependent manner, interleukin 6 production. This effect was reduced when protein kinase A was blocked by KT-5720; it was not affected by calphostin C, a protein kinase C inhibitor. Forskolin caused a concentration-dependent increase in interleukin 6 release that was also inhibited by KT-5720. Because prostaglandins are believed to play a role in interleukin 6 production, we tried to determine whether the stimulatory effects of vasoactive intestinal peptide and forskolin on cytokine release might be mediated by stimulation of prostaglandin production in cortical astrocytes. Vasoactive intestinal peptide did not increase the production of either prostaglandin E2 or F2 alpha. Conversely, forskolin concentration-dependently stimulated the production of both prostaglandins, an effect that was blocked by indomethacin. Indomethacin did not affect either vasoactive intestinal peptide- or forskolin-stimulated interleukin 6 production. To exclude the possibility that prostaglandins participate in interleukin 6 production induced by forskolin, we tested prostaglandins E2 and F2 alpha. The former was completely ineffective in eliciting the cytokine production, whereas prostaglandin F2 alpha slightly increased interleukin 6 production only at the highest concentrations. 8-Bromo-cAMP and dibutyryl-cAMP stimulated interleukin 6 production to a lesser extent than vasoactive intestinal peptide and forskolin. In conclusion, we provide evidence that vasoactive intestinal peptide increases interleukin 6 production by astrocytes through the stimulation of the cAMP-protein kinase A pathway, an effect that is reproduced by cAMP analogues.(ABSTRACT TRUNCATED AT 250 WORDS)
在本研究中，我们分析了环磷酸腺苷（cAMP）-蛋白激酶A系统在调控培养的皮质星形胶质细胞白细胞介素6产生中的作用。血管活性肠肽以剂量依赖的方式显著增加白细胞介素6的产生。当蛋白激酶A被KT-5720阻断时，这种作用减弱；它不受蛋白激酶C抑制剂钙泊三醇C的影响。福斯可林引起白细胞介素6释放呈浓度依赖性增加，这也被KT-5720抑制。由于前列腺素被认为在白细胞介素6的产生中起作用，我们试图确定血管活性肠肽和福斯可林对细胞因子释放的刺激作用是否可能通过刺激皮质星形胶质细胞中前列腺素的产生来介导。血管活性肠肽既不增加前列腺素E2也不增加F2α的产生。相反，福斯可林浓度依赖性地刺激这两种前列腺素的产生，这种作用被吲哚美辛阻断。吲哚美辛不影响血管活性肠肽或福斯可林刺激的白细胞介素6的产生。为排除前列腺素参与福斯可林诱导的白细胞介素6产生的可能性，我们测试了前列腺素E2和F2α。前者在引发细胞因子产生方面完全无效，而前列腺素F2α仅在最高浓度时略微增加白细胞介素6的产生。8-溴-cAMP和二丁酰-cAMP刺激白细胞介素6产生的程度低于血管活性肠肽和福斯可林。总之，我们提供证据表明血管活性肠肽通过刺激cAMP-蛋白激酶A途径增加星形胶质细胞白细胞介素6的产生，cAMP类似物可重现这种作用。（摘要截断于250字）
