Tributyltin (TBT) Increases TNF $\alpha$ mRNA Expression and Induces Apoptosis in the Murine Macrophage Cell Line in Vitro

ABSTRACT

Objective: Tributyltin (TBT) compounds have been widely used as antifouling agents for ship-bottom paint. The immune system is a target of TBT intoxication. We evaluated the effects of TBT chloride in macrophages, which have critical roles in the immune system, using a murine macrophage lineage cell line, J774.1, in vitro. Methods: We examined tumor necrosis factor α (TNF α), interleukin-1β (IL-1β) and c-jun mRNA expression in J774.1 cells. The effects of TBT on the apoptosis of J774.1 cells were examined by determining the percentage of TUNEL-positive cells and caspase-3 activity. Results: The mean values of the viabilities of J774.1 cells exposed to TBT decreased dose-dependently. The relative mRNA expression of TNFα increased dose-dependently, however, that of IL-1β was not significantly different among the groups. The mean percentage of TUNEL-positive cells increased dose-dependently. Increases in the caspase-3 activities of J774.1 cells were observed in the groups exposed to higher concentrations of TBT. The mean value of relative mRNA expression of c-Jun transcription factor increased dose-dependently. Conclusions: The increases in the percentage of TUNEL-positive cells and in caspase-3 activity suggested that exposure to TBT induces apoptosis of J774.1 cells. The increases in the mRNA expression of TNFα and c-jun by TBT may be related to apoptosis in macrophages.