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Zip14 expression induced by lipopolysaccharides in macrophages attenuates inflammatory response

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Abstract

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.

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Acknowledgments

This work was supported by the Biomedical Research Council, Agency for Science, Technology and Research, Singapore.

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Authors and Affiliations

  1. Institute Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Singapore, 138673, Singapore

    Ahmed Sayadi, Anh-Tuan Nguyen, Frederic A. Bard & Emilie A. Bard-Chapeau

  2. Department of Biochemistry, National University of Singapore, 8 Medical Drive, Blk MD7, Singapore, 117597, Singapore

    Frederic A. Bard

Authors
  1. Ahmed Sayadi
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  2. Anh-Tuan Nguyen
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  3. Frederic A. Bard
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  4. Emilie A. Bard-Chapeau
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Corresponding author

Correspondence to Emilie A. Bard-Chapeau.

Additional information

Responsible Editor: Liwu Li.

A. Sayadi and A.-T. Nguyen contributed equally to this work.

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Sayadi, A., Nguyen, AT., Bard, F.A. et al. Zip14 expression induced by lipopolysaccharides in macrophages attenuates inflammatory response. Inflamm. Res. 62, 133–143 (2013). https://doi.org/10.1007/s00011-012-0559-y

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  • DOI: https://doi.org/10.1007/s00011-012-0559-y

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