Conclusions
Collectively, our results identified the zinc transporter Zip14 as expressed downstream of lipopolysaccharide signals in macrophages. Zip14 induction had a regulatory function in cytokine production.
Methods
Primary macrophages were subjected to treatments with lipopolysaccharides, cytokines, chemicals, and pharmacological agents. SLC39A14 and inflammatory cytokine gene expressions were assessed by RT-qPCR. Zip14 siRNA knockdown was performed to explore the gene function.
Results
Lipopolysaccharide's inflammatory stimulus was a strong inducer of SLC39A14 mRNA expression in macrophages. This induction was dependent on calcium signaling, GC-rich DNA-binding, and NF-κB down-regulation. Impregnation of lipopolysaccharide-stimulated macrophages with the glucocorticoid dexamethasone further enhanced Zip14 expression while reducing interleukin-6 and tumor necrosis factor-α production. Zip14 knockdown in macrophages attenuated the expression and secretion of cytokines, indicating a buffering function for this zinc transporter. Conclusions: Collectively, our results identified the zinc transporter Zip14 as expressed downstream of lipopolysaccharide signals in macrophages. Zip14 induction had a regulatory function in cytokine production.