Liquid perfluorochemical inhibits inducible nitric oxide synthase expression and nitric oxide formation in lipopolysaccharide-treated RAW 264.7 macrophages.
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.
Chang
Li-Ping
LP
Department of Radiation Oncology, Tri-Service General Hospital, Taipei, Taiwan.
Lai
Yuan-Shu
YS
Wu
Chang-Jer
CJ
Chou
Tz-Chong
TC
D000818:Animals; D002460:Cell Line; D003470:Culture Media / Q000032:analysis / Q000737:chemistry; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D005466:Fluorocarbons / Q000378:metabolism* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009573:Nitrites / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
D003470:Culture Media; D016207:Cytokines; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005466:Fluorocarbons; D008070:Lipopolysaccharides; D009573:Nitrites; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C429307:fluorocarbon 77; D009569:Nitric Oxide; C037631:2',7'-dichlorofluorescein; D052247:Nitric Oxide Synthase Type II