Influences of rapamycin on phenotype and function of rat bone marrow-derived dendritic cells in

Abstract

Objective To observe the effect of rapamycin (RAPA) on the phenotype and functional activities of dendritic cells (DC) in vitro.Methods Bone marrow mononuclear cells of Lewis rats were induced and differentiated in vitro.On the day 6,lipopolysaccharide (LPS) and 10 μg/L or 100 μg/L RAPA were added to the culture concomitantly.Fourty-eight h later,co-stimulatory molecule expression,apoptosis,intedeukin (IL) -12 and IL-10 levels in the supematant were detected.Mixed lymphocyte reaction (MLR) was performed.Brown Norway rat splenocytes were used as responders.Results RAPA significantly inhibited the up-regulated expression of co-stimulatory molecules.RAPA induced DC apoptosis.The increased production of IL-10 and IL-12 by DC in response to LPS was decreased in the presence of PAPA [from (1533 ±117) ng/L and (2575 ±58) ng/L to (330 ±159) ng/L and (245 ±63) ng/L in the presence of 100 μg/L RAPA,respectively].Moreover,DC treated with PAPA had an inhibitory effect on T cell proliferation in MLR.Conclusion PAPA impacts the phenotypic maturation,induces apoptosis,inhibits cytokine production,and inhibits the allostimulatory activity of DC. Key words: Dendritic cells; Rapamycin; Cytokines; Mixed lymphocyte reaction