Zip14 expression induced by lipopolysaccharides in macrophages attenuates inflammatory response
2013 (English)In: Inflammation Research, ISSN 1023-3830, E-ISSN 1420-908X, Vol. 62, no 2Article in journal (Refereed) Published
OBJECTIVE AND DESIGN: We investigated the role and regulation of zinc transporters in the activation of the inflammatory response in macrophages. Our exploratory computational study found that Zip14 (SLC39A14) was consistently up-regulated in activated macrophages; we therefore focused subsequently on that gene in the mechanistic study.
MATERIAL: The expression and function of Zip14 was assessed in primary macrophages obtained by in-vitro differentiation of monocytes from human blood.
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.
Place, publisher, year, edition, pages
2013. Vol. 62, no 2
Rheumatology and Autoimmunity
IdentifiersURN: urn:nbn:se:uu:diva-282511DOI: 10.1007/s00011-012-0559-yPubMedID: 23052185OAI: oai:DiVA.org:uu-282511DiVA: diva2:917132