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 microg/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 E2(PGE2), tumor necrosis factor alpha (TNF-alpha), and interleukins (IL)-1beta, -6), and -10 were measured in medium. Alterations in cyclooxygenase (COX) 2 expression and nuclear transcription factor (NF) kappaB activation in cells were also evaluated.


RESULTS
Pre- or posttreatment with FC-77 dose-dependently reduced the LPS-induced TNF-alpha, IL-1beta, and IL-6 formation and enhanced IL-10 production compared to LPS-stimulated alone cells. FC-77 also attenuated the LPS-induced PGE2 formation accompanied by suppressing COX-2 expression, the degradation of cytosolic inhibitor of kappaB-alpha and NF-kappaB activation.


CONCLUSIONS
FC-77 inhibits inflammatory responses in LPS-stimulated macrophages by a mechanism that involves the attenuation of NF-kappaB dependent induction of COX-2/PGE2 pathway and the pro- /anti-inflammatory cytokine ratio.
Chang
Hung
H
Department of Surgery, Tri-Service General Hospital, Taipei, Taiwan, R.O.C.
Kuo
Fu-Chang
FC
Lai
Yuan-Shu
YS
Chou
Tz-Chong
TC
D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000096:biosynthesis*; D005466:Fluorocarbons / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism
D016207:Cytokines; D005466:Fluorocarbons; D008070:Lipopolysaccharides; C429307:fluorocarbon 77; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases