Perfluorocarbon Suppresses Lipopolysaccharide- and α-Toxin-Induced Interleukin-8 Release from Alveolar Epithelial Cells

Abstract

Background/Aims: Human pulmonary alveolar epithelial (A549) cells release interleukin-8 (IL-8) on stimulation by lipopolysaccharide (LPS) and α-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 α-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 α-toxin. PFC may be useful clinically in treatment of pulmonary inflammation in the alveolar space.

Cytoprotection of Perfluorocarbon on PMVECs In Vitro

“…One possibility is that a dense, immiscible PFC liquid with a high spreading coefficient could form a physical protective barrier, thus shielding target cells from various proinflammatory mediators as suggested by the cell culture experiments described here. Evidence for this barrier effect is supported by other studies [21,22]. Another mechanism implicated in the biological effects of PFC is related to the fact that PFC is able to partition into the lipid component of cellular membranes and the cytoplasm [23], where PFC can execute its nonspecific cell membrane stabilization by interfering with (1) the interaction between stimulant and receptor, (2) the transmembrane signal transduction, and (3) the transduction of intracellular signaling pathways [23][24][25].…”

Anti-inflammatory effects of perfluorocarbon compounds

“…Transwell experiments (FIGURE 1A) with monolayers of human cell lines have been used to simulate the air-tissue interface present in vivo and to study the effect of PFCs on IL-8 release [80][81][82]. Studies with the A549 cell line have shown that 24-h incubation with PFOB or FC-84 prevents the release of IL-8 after addition of TNF-α, LPS or α-toxin by acting as a physical barrier [80,82].…”

The effects of perfluorocarbon on ICAM-1 expression in LPS-induced A549 cells and the potential mechanism

“…In recent years, the major studies regarding liquid ventilation have focused on animal experiments or in vitro experiments with few clinical trials. Based on these animal studies and cell experiments, liquid ventilation holds promise to improve low pulmonary compliance and gas exchange in addition to reducing pulmonary inflammatory responses, and ultimately improving the prognosis of animals with ARDS (6)(7)(8)(9)(10)(11)(12)(13)(14). However, the results of clinical randomized controlled trials (RCTs) and basic research have produced conflicting results, and the outlook of liquid ventilation has been disappointing.…”

“…The majority of patients require endotracheal intubation and positive pressure ventilation (1,2) and account for millions of days spent in intensive care units (5). In recent years, treatments of ALI/ARDS with improved efficacy have been sought, and studies have indicated that liquid ventilation with perfluorocarbon (PFC) compounds is a promising therapeutic approach (6)(7)(8)(9)(10)(11)(12)(13)(14). PFC is of interest for the treatment of ALI/ARDS due to the unique physicochemical properties, such as high solubility for oxygen, and the anti-inflammatory effects.…”

“…Liquid ventilation or aerosolized PFC has been demonstrated to improve gas exchange and improve pulmonary compliance compared with conventional mechanical ventilation in a variety of animal models of ALI/ARDS (6)(7)(8). Specifically, PFC has been shown to reduce levels of cytokines, chemokines and other mediators of pulmonary inflammation in both in vivo and in vitro models (9)(10)(11)(12)(13)(14). However, the understanding of the underlying mechanisms remains poor, in particular of the mechanisms associated with the PFC-induced anti-inflammatory effects.…”