Developmental endothelial locus-1 inhibits MIF production through suppression of NF-κB in macrophages

  • Authors:
    • Seung-Hwan Lee
    • Dong-Young Kim
    • Yoon-Young Kang
    • Hyesoon Kim
    • Jungin Jang
    • Mi-Ni Lee
    • Goo Taeg Oh
    • Sang-Wook Kang
    • Eun Young Choi
  • View Affiliations

  • Published online on: February 5, 2014     https://doi.org/10.3892/ijmm.2014.1645
  • Pages: 919-924
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Abstract

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that regulates leukocyte recruitment, thereby playing a pivotal role in the regulation of innate and adaptive immunity and tumor progression. Elevated levels of MIF are associated with numerous inflammatory disorders and cancers. To determine whether developmental endothelial locus-1 (Del-1) regulated MIF, RAW264.7 macrophages were treated with Del-1 and assessed using ELISA. The results showed that MIF was downregulated in macrophages by Del-1, an endogenous anti-inflammatory protein that was previously shown to limit leukocyte adhesion and migration. Treatment of RAW264.7 macrophages with Del-1 inhibited constitutive and lipopolysaccharide (LPS)-induced MIF secretion. Recombinant Del-1 protein attenuated the phosphorylation of IκBα induced by a relatively low concentration of LPS in THP-1 monocytes, but did not inhibit IκBα phosphorylation in response to a relatively high concentration of LPS. Concomitantly, translocation of NF-κB to the nucleus was inhibited by Del-1 in LPS-activated macrophages. In addition, conditioned medium harvested from cells transfected with a Del-1 expression plasmid suppressed NF-κB activation in response to relatively low concentrations of TNF-α, albeit not the activation that was induced by a relatively high concentration of TNF-α. On the other hand, although Del-1 enhanced the macrophage expression of p53, a known negative regulator of MIF production, MIF production was not significantly affected by the level of p53 in mouse bone marrow-derived macrophages. These findings suggested that Del-1 controls NF-κB-activated MIF production in macrophages, and the potential application of Del-1 to therapeutic modalities for chronic inflammation-associated cancers.
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2014-April
Volume 33 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Lee S, Kim D, Kang Y, Kim H, Jang J, Lee M, Oh GT, Kang S and Choi EY: Developmental endothelial locus-1 inhibits MIF production through suppression of NF-κB in macrophages . Int J Mol Med 33: 919-924, 2014.
APA
Lee, S., Kim, D., Kang, Y., Kim, H., Jang, J., Lee, M. ... Choi, E.Y. (2014). Developmental endothelial locus-1 inhibits MIF production through suppression of NF-κB in macrophages . International Journal of Molecular Medicine, 33, 919-924. https://doi.org/10.3892/ijmm.2014.1645
MLA
Lee, S., Kim, D., Kang, Y., Kim, H., Jang, J., Lee, M., Oh, G. T., Kang, S., Choi, E. Y."Developmental endothelial locus-1 inhibits MIF production through suppression of NF-κB in macrophages ". International Journal of Molecular Medicine 33.4 (2014): 919-924.
Chicago
Lee, S., Kim, D., Kang, Y., Kim, H., Jang, J., Lee, M., Oh, G. T., Kang, S., Choi, E. Y."Developmental endothelial locus-1 inhibits MIF production through suppression of NF-κB in macrophages ". International Journal of Molecular Medicine 33, no. 4 (2014): 919-924. https://doi.org/10.3892/ijmm.2014.1645