抄録
A metal chelator diethylenetriaminepentaacetic acid (DTPA) has been reported to inhibits replication of human cytomegalovirus (hCMV). In the investigation of the mechanism of DTPA-induced antiviral effect, we found that zinc-regulated expression of metallothionein (MT) enhances promoter activity of hCMV major immediate early gene through the activation of a transcriptional factor NF-κB. Number of endogenous NF-κB-regulated genes have been identified. Modulation of the expression of endogenous NF-κB-regulated gene by zinc and/or MT was investigated in vitro and in vivo. Zinc induces macrophage colony stimulating factor (M-CSF) in L929 fibroblast, MC3T3-E1 osteoblast, and lung fibroblast from MT+/+ wild-type mouse, but not in MT−/− lung fibroblast. Overexpression of MT in L929 cells increases NF-κB-DNA binding and expression of M-CSF. NF-κB is a major signaling protein in lipopolysaccharide (LPS)-induced activation of macrophage. LPS-induced expression of inflammatory cytokines, TNF, IL-1, and IL-6, was lower in MT−/− macrophage than MT+/+ wild-type. Zinc and MT act as an important modulator of cytokines such as M-CSF, TNF, IL-1, and IL-6. The functions of zinc and MT in inflammation and immunoresponse should be further investigated in detail.
