title: Chronic non-bacterial osteomyelitis is associated with impaired Sp1 signaling, reduced IL10 promoter phosphorylation, and reduced myeloid IL-10 expression.
abstract: Chronic non-bacterial osteomyelitis (CNO) is an auto-inflammatory disorder that affects the skeletal system. Interleukin (IL-)10 is an immune-modulatory cytokine that controls inflammation, and limits inflammatory cytokine responses. Dysregulation of IL-10 expression has been shown to result in autoimmune and infectious diseases. We investigated IL-10 expression by monocytic cells from CNO patients and controls. In response to stimulation with LPS, IL-10 expression from CNO monocytes was reduced (p<0.001). This was independent of IL10 promoter polymorphisms. Thus, we investigated Sp1 recruitment to the IL10 promoter and saw markedly reduced binding in CNO monocytes. This was accompanied with reduced phosphorylation of histone H3 serine 10 (H3S10), an activating epigenetic mark. Impaired recruitment of Sp1 to the IL10 promoter, and reduced H3S10 phosphorylation, may be a reflection of deficient MAPK signaling in CNO monocytes in response to LPS stimulation. Thus, we have discovered a mechanism that may be central in the pathophysiology of CNO.
authors.affiliation: Klinik und Poliklinik für Kinder- und Jugendmedizin, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, D-01307 Dresden, Germany.
authors.forename: S R
authors.initials: SR
authors.lastname: Hofmann
authors.forename: T
authors.initials: T
authors.lastname: Schwarz
authors.forename: J C
authors.initials: JC
authors.lastname: Möller
authors.forename: H
authors.initials: H
authors.lastname: Morbach
authors.forename: A
authors.initials: A
authors.lastname: Schnabel
authors.forename: A
authors.initials: A
authors.lastname: Rösen-Wolff
authors.forename: H J
authors.initials: HJ
authors.lastname: Girschick
authors.forename: C M
authors.initials: CM
authors.lastname: Hedrich
mesh_terms: D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D006657:Histones / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000276:immunology*; D010019:Osteomyelitis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D010766:Phosphorylation; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D006657:Histones; C508609:IL10 protein, human; D008070:Lipopolysaccharides; D016329:Sp1 Transcription Factor; D016753:Interleukin-10