title: KLF4 modulates expression of IL-6 in dendritic cells via both promoter activation and epigenetic modification.
abstract: The initiation and maintenance of the immune response require a coordinated regulation of signal transduction pathways. Identifying the mechanisms by which these pathways are controlled and modulated is a significant goal of immunology. In the present report, we show a novel role for the zinc finger transcription factor Kruppel-like factor 4 (KLF4) in the modulation of the inflammatory immune response via its regulation of IL-6. We analyzed the role of KLF4 in the production of IL-6 by dendritic cells. Our data indicate that KLF4 can act in a dual function manner. It acts as a transcription factor in that it can bind to and activate the IL-6 promoter at specific binding sites. KLF4 also has a role in the chromatin remodeling of the IL-6 promoter in that cells deficient in KLF4 exhibited a relative hypoacetylation. These results indicate a molecular role for KLF4 in modulating the intensity of the inflammatory response and help to explain its pleiotropic role in different settings.
authors.affiliation: Departments of Neurology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Rosenzweig
authors.forename: Justin D
authors.initials: JD
authors.lastname: Glenn
authors.forename: Peter A
authors.initials: PA
authors.lastname: Calabresi
authors.forename: Katharine A
authors.initials: KA
authors.lastname: Whartenby
mesh_terms: D000107:Acetylation; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016384:Consensus Sequence / Q000235:genetics; D003713:Dendritic Cells / Q000378:metabolism; D044127:Epigenesis, Genetic; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D015850:Interleukin-6; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D016328:NF-kappa B; D050796:STAT3 Transcription Factor
keywords: Cytokine; Dendritic Cells; IL-6; Inflammation; KLF4; Kruppel-like factor (KLF); Monocytes