Effect of Gas6 in silica-induced inflammation on differentiated human acute monocytic leukemia (THP-1) macrophages

Abstract

Objective: To investigate the modulation role of Gas6 in silica-induced inflammatory effect on human macrophages. Methods: Differentiated THP-1 macrophages were exposed to different concentrations of silica for 6 h and 24 h. Additionally, silica-activated macrophages were treated with different concentrations of recombine human Gas6 and Gas6 antibody respectively. Cell viabilities were determined by CCK-8 kit. Expression levels of Gas6 and inflammatory cytokines (TNF-α, IL-1β and IL-6) were measured by ELISA assay kits. Results: Silica particles induced clear dose-dependent decreases of cell viability and Gas6 expression at both 6 h and 24 h. The cell viability of 24 h is lower than 6 h at the same concentration of silica (P<0.05). Furthermore, silica activated macrophages treated with Gas6 antibody induced significant decreases of Gas6 both at 6 h and 24 h (P<0.05). After pretreated with various concentrations of Gas6 antibody, silica induced higher expressions of inflammatory cytokines (TNF-α, IL-1β, IL-6) in dose-dependent manners at two time points. Addition of exoge-nous Gas6 significantly suppressed silica-induced inflammatory cytokines concentrations mentioned above in the cell culture supernatants in clear dose-dependent manners. Conclusion: Exogenous Gas6 could inhibit the secre-tion of inflammatory cytokines in macrophages, while the block of Gas6 might enhance this inflammation.