Modulation of phenotypic and functional maturation of murine bone-marrow-derived dendritic cells (BMDCs) induced by cadmium chloride

Abstract

Cadmium (Cd(2+)) has been classified as a type I human carcinogen by the International Agency for Research on Cancer. In the present study, we are going to report for the first time on the detailed modulation of phenotypic and functional maturation of murine bone marrow-derived dendritic cells (BMDCs) induced by cadmium chloride. Dendritic cells (DCs) are major modulators in the whole immune system. One dynamic field of research is the manipulation of DCs as pharmacological targets to screen novel biological modifiers for the treatment of tumor, inflammatory and autoimmune disorders. Phenotypic and functional maturation of BMDCs was evaluated by phase-contrast light microscope for primary cultures, flow cytometry (FCM) for important DC markers, reverse-transcriptase PCR and enzyme linked immunosorbent assay (ELISA) for cytokines. Cd(2+)-induced BMDC death was also performed by comet assay. Our results elucidated that Cd(2+) suppressed maturation of BMDCs via changes as reflected by the decreased expression of key surface molecules such as MHCII and CD40, and also by releasing the lower level of IL-12p70. The change of expression of other co-stimulatory molecules such as CD86 and CD80 was not so significant. However, it was found that cadmium promotes releasing a higher level of IL-23 from BMDCs. So from our study, it can be concluded that cadmium may be one of the potent immunosuppressive agents through the blockage of DC maturation and function.