Ethyl pyruvate modulates adhesive and secretory reactions in human lung epithelial cells.
OBJECTIVE
Ethyl pyruvate (EtP) may prolong survival and ameliorate organ dysfunction in a variety of models of critical illness, e.g. severe sepsis and acute respiratory syndrome, by modulation of the expression of inflammatory mediators. Here, we studied the effects of EtP on the reactions in and between human neutrophils and lung epithelial (A549) cells in vitro.


METHODS
Neutrophil adhesion to, surface expression of ICAM-1 and VCAM-1 on, and release of IL-8 and G-CSF from A549 cells were measured by ELISA after stimulation with IL-1 beta or TNFalpha.


RESULTS
After treatment of A549 cells with EtP, a substantial reduction in the cytokine-induced adhesion of neutrophils to monolayers was noted, whereas sodium pyruvate (NaP) conferred no reduction. Likewise, treatment with 2.5-10 mM EtP (but not NaP) reduced ICAM-1 and VCAM-1 expression in a dose-dependent fashion. The generation of cytokines of significance for adhesive and proliferative events in host defense, IL-8 and G-CSF, was also potently impaired by EtP.


CONCLUSIONS
Exposure of lung epithelial cells to 2.5-10 mM EtP inhibited the generation of inflammatory-regulating cytokines IL-8 and G-CSF, reduced ICAM-1 and VCAM-1 expression and impeded the adhesiveness of neutrophils to lung epithelial cells. These are reactions of significance for early inflammatory responses in the lung, suggesting a role for EtP as a treatment for acute pulmonary conditions.
Johansson
Anne-Sofie
AS
Center for Inflammation and Hematology Research, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden. anne-sofie.johansson@ki.se
Palmblad
Jan
J
D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D016179:Granulocyte Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000502:physiology; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011773:Pyruvates / Q000494:pharmacology*; D020545:Respiratory Mucosa / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D053583:Interleukin-1beta; D016209:Interleukin-8; D011773:Pyruvates; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C046522:ethyl pyruvate; D018799:Intercellular Adhesion Molecule-1; D016179:Granulocyte Colony-Stimulating Factor