Perfluorocarbon suppresses lipopolysaccharide- and alpha-toxin-induced interleukin-8 release from alveolar epithelial cells.
OBJECTIVE
Human pulmonary alveolar epithelial (A549) cells release interleukin-8 (IL-8) on stimulation by lipopolysaccharide (LPS) and alpha-toxin. We hypothesised that the perfluorocarbons (PFCs), perflubron and FC-84, would block stimulation of A549 cells by these toxins.


METHODS
The levels of IL-8 production in A549 cells were measured following exposure to toxins for 24 h with or without PFC. The amount of IL-8 released from A549 cells was measured by enzyme-linked immunosorbent assay, and the level of IL-8 mRNA was measured by real-time RT-PCR.


RESULTS
When stimulated with LPS or alpha-toxin, IL-8 release from A549 cells increased. There were no significant differences in level of IL-8 release between cells pre-incubated for 24 h with or without PFC after toxin stimulation for 24 h. When PFC was administered along with LPS stimulation, the level of IL-8 release was decreased (LPS control, 1,398 +/- 110 pg/well; FC-84, 686 +/- 50 pg/well; perflubron, 749 +/- 137 pg/well; p < 0.05). Levels of IL-8 mRNA expression were significantly higher with than without LPS, and those with LPS and perflubron were significantly lower than those with LPS alone.


CONCLUSIONS
The results show that PFCs block stimulation of A549 cells by LPS or alpha-toxin. PFC may be useful clinically in treatment of pulmonary inflammation in the alveolar space.
Nakata
Setsuko
S
Department of Pediatrics, Shinshu University School of Medicine, Nagano, Japan.
Yasui
Kozo
K
Nakamura
Tomohiko
T
Kubota
Noriko
N
Baba
Atsushi
A
D001802:Blood Substitutes / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005466:Fluorocarbons / Q000494:pharmacology*; D006801:Humans; D006842:Hydrocarbons, Brominated; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D010738:Type C Phospholipases / Q000494:pharmacology*
D001802:Blood Substitutes; D004338:Drug Combinations; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D010738:Type C Phospholipases; C003072:perflubron