Abstract
Immunological functions are impaired in individuals who chronically exposed to arsenicals from arsenic-polluted underground water from well, thereby suggesting that arsenic affect immune systems. However, little is known that chronic exposure to arsenic affect physiological function of mast cells. Here we show that exposure of rat RBL-2H3 mast cells to 0.5 and 1 μM arsenite (As(III)) for 14 and 28 days as a chronic exposure reduce the degranulation and the increase in cellular Ca2+ concentration induced with ovalbumin and anti-ovalbumin (OA/anti-OA). In order to investigate the mechanisms underlying the inhibition effect of As(III) on OA/anti-OA-induced degranulation, we measured the effect of chronic As(III) exposure on the degranulation induced by A23187, Ca2+ ionophore and thapsigargin (TG), store-operated calcium entry (SOCE) inducer. The results indicated that exposure of RBL-2H3 cells to chronic As(III) exposure inhibits the TG-induced degranulation, but not A23187. It is known that interaction of stromal interaction molecule1 (STIM1) with calcium release-activated calcium modulator1 (Orai1) or transient receptor potential canonical channels (TRPC) on the plasma membrane is required for SOCE. Thus, we measured mRNA and protein levels of those in involved in SOCE after exposure to As(III). The results indicated that TRPC5 expression is down-regulated in RBL-2H3 cells exposed to As(III). In this study, we suggested that exposure of RBL-2H3 cells to As(III) impair OA/anti-OA-induced degranulation accompanied by a decrease in SOCE, and we suggest that the down-regulation of TRPC5 is, at least in part, relevant to the impairment of SOCE by exposure to As(III).
