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

Seung Hwan Lee, Dong Young Kim, Yoon Young Kang, Hyesoon Kim, Jungin Jang, M. I.N.I. Lee, Goo Taeg Oh, Sang Wook Kang, Eun Young Choi

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish
Pages (from-to)919-924
Number of pages6
JournalInternational Journal of Molecular Medicine
Volume33
Issue number4
DOIs
StatePublished - Apr 2014

Keywords

  • Developmental endothelial locus-1
  • Inflammation
  • Innate immunity
  • Macrophage
  • Macrophage migration inhibitory factor

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