Inhibition of inflammatory responses by FC-77, a perfluorochemical, in lipopolysaccharide-treated RAW 264.7 macrophages

Objective: This study tested whether FC-77, a perfluorochemical, inhibits inflammatory responses in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophages. The possible anti-inflammatory mechanisms involved were also investigated. Methods: RAW 264.7 macrophages were simultaneously incubated with pure FC-77 at final volume of 10% or 30% (v/v) and LPS (1 mu g/ml) for 12 or 24 h on a mechanical shaker. In some tests FC-77 was added after cells stimulated by LPS for 12 h. Then the levels of prostaglandin E-2 (PGE(2)), tumor necrosis factor alpha (TNF-alpha), and interleukins (IL)-1 beta, -6), and -10 were measured in medium. Alterations in cyclooxygenase (COX) 2 expression and nuclear transcription factor (NF) kappa B activation in cells were also evaluated. Results: Pre- or posttreatment with FC-77 dose-dependently reduced the LPS-induced TNF-alpha, IL-1 beta, and IL-6 formation and enhanced IL-10 production compared to LPS-stimulated alone cells. FC-77 also attenuated the LPS-induced PGE(2) formation accompanied by suppressing COX-2 expression, the degradation of cytosolic inhibitor of kappa B-alpha and NF-kappa B activation. Conclusions: FC-77 inhibits inflammatory responses in LPS-stimulated macrophages by a mechanism that involves the attenuation of NF-kappa B dependent induction of COX-2/PGE(2) pathway and the pro- /anti-inflammatory cytokine ratio.