Department of Radiation Oncology, Tri-Service General Hospital, Taipei, Taiwan.
J Pharmacol Sci. 2009 Oct;111(2):147-54. doi: 10.1254/jphs.09043fp.
Partial liquid ventilation with various types of perfluorocarbon (PFC) has been shown to be beneficial in treating acute lung injury, a clinical outcome that may involve the anti-inflammatory activity of PFC. FC-77 is a type of PFC with relatively higher vapor pressure and evaporative loss than other PFCs during partial liquid ventilation. Overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been proposed to play a crucial role in the pathogenesis of inflammatory diseases. However, whether the iNOS/NO pathway is affected by FC-77 is unknown. Thus, the aim of this study was to investigate whether FC-77 inhibits iNOS expression and NO production in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. We found that treatment with FC-77 significantly attenuated LPS-induced iNOS expression/activity and production of NO and reactive oxygen species (ROS). FC-77 also attenuated LPS-induced pro-inflammatory cytokine formation, but enhanced interleukin-10 production. Furthermore, the LPS-induced degradation of cytosolic IkappaB-alpha and activation of nuclear transcription factor-kappaB (NF-kappaB) were also inhibited by FC-77. In conclusion, the present study is the first to demonstrate that FC-77 decreases LPS-induced NO production in macrophages, which may be associated with the suppression of pro-inflammatory cytokines, and ROS production, as well as NF-kappaB activation. These results also provide a novel explanation for its anti-inflammatory activity.
部分液体通气与各种类型的全氟化碳(PFC)已被证明是有益的治疗急性肺损伤,这一临床结果可能涉及的抗炎活性的 PFC。FC-77 是一种 PFC 与相对较高的蒸气压和蒸发损失比其他 PFC 在部分液体通气。一氧化氮(NO)的产生过多由诱导型一氧化氮合酶(iNOS)被提出在炎症性疾病的发病机制中起关键作用。然而,是否 iNOS/NO 途径受到 FC-77 的影响尚不清楚。因此,本研究的目的是探讨 FC-77 是否抑制 LPS 诱导的 RAW 264.7 巨噬细胞中 iNOS 的表达和 NO 的产生。我们发现,FC-77 处理显著减弱 LPS 诱导的 iNOS 表达/活性和 NO 和活性氧(ROS)的产生。FC-77 也减弱 LPS 诱导的促炎细胞因子的形成,但增强白细胞介素-10 的产生。此外,LPS 诱导的胞质 IkappaB-alpha 的降解和核转录因子-kappaB(NF-kappaB)的激活也被 FC-77 抑制。总之,本研究首次表明 FC-77 减少 LPS 诱导的巨噬细胞中 NO 的产生,这可能与抑制促炎细胞因子和 ROS 的产生,以及 NF-kappaB 的激活有关。这些结果也为其抗炎活性提供了新的解释。