title: Developmental endothelial locus-1 inhibits MIF production through suppression of NF-κB in macrophages.
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.
authors: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Seung-Hwan
authors: SH
authors: Lee
authors: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Dong-Young
authors: DY
authors: Kim
authors: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Yoon-Young
authors: YY
authors: Kang
authors: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Hyesoon
authors: H
authors: Kim
authors: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Jungin
authors: J
authors: Jang
authors: Division of Life Sciences, Ewha Womans University, Seoul, Republic of Korea.
authors: Mi-Ni
authors: MN
authors: Lee
authors: Division of Life Sciences, Ewha Womans University, Seoul, Republic of Korea.
authors: Goo Taeg
authors: GT
authors: Oh
authors: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Sang-Wook
authors: SW
authors: Kang
authors: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Eun Young
authors: EY
authors: Choi
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D002460:Cell Line; D005110:Extracellular Space / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D042541:Intracellular Space / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C491706:Edil3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse