| 17304101 |
Pearl-Yafe M, Fabian I, Halperin D, Flatau E, Werber S, Shalit I: Interferon-gamma and bacterial lipopolysaccharide act synergistically on human neutrophils enhancing interleukin-8, interleukin-1beta, tumor necrosis factor-alpha, and interleukin-12 p70 secretion and phagocytosis via upregulation of toll-like receptor 4. Shock. 2007 Mar;27(3):226-31.
In human neutrophils, interferon (IFN)-gamma enhanced the expression of toll-like receptor 4 (TLR4), a crucial component of the signaling receptor complex for bacterial lipopolysaccharide (LPS). Lipopolysaccharide alone did not affect TLR4 expression, but costimulation with IFN-gamma and LPS induced higher levels of TLR4 expression than stimulation with IFN-gamma alone. Using the protein synthesis inhibitor cycloheximide and measuring the expression of CD35 in neutrophils stimulated with IFN-gamma and LPS alone or in combination, we could demonstrate that IFN-gamma enhances TLR4 by de novo protein synthesis, whereas the addition of LPS acts synergistically by enhancing vesicular mobilization to the cell surface. Costimulation with IFN-gamma and LPS induced neutrophil activation and enhanced secretion of the cytokines, interleukin (IL)-8, IL-1beta, tumor necrosis factor-alpha, and IL-12 p70, and phagocytosis of latex beads, processes that were blocked by a monoclonal antibody specific for TLR4. These data suggest that IFN-gamma primes neutrophils to respond to LPS. |
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