title: Adrenomedullin RegulatesIL-1βGene Expression in F4/80+ Macrophages during Synovial Inflammation.
abstract: Adrenomedullin (AM) plays an important role in the regulation of inflammatory processes; however, the role and expression of AM in synovial inflammation have not been determined. To investigate the expression and role of AM in inflamed synovial tissue (ST), the gene expression profiles of AM in the ST, including synovial macrophages and fibroblasts, of a murine patellar surgical dislocation model were characterized. In addition, the effects of interleukin-(IL-) 1βand AM in cultured synovial cells were also examined. CD11c+macrophages were found to be elevated in ST of the surgically dislocated patella. Higher gene expression ofCD11c,IL-1β,AM, receptor activity-modifying proteins 2(RAMP2), and 3(RAMP3)was also observed in ST obtained from the dislocated side.AMexpression was also significantly increased in synovial fibroblasts and macrophages in response to IL-1βtreatment. Synovial macrophages also highly expressedRAMP3compared to fibroblasts and this expression was further stimulated by exogenously added IL-1β. Further, the treatment of the F4/80-positive cell fraction obtained from ST with AM inhibitedIL-1βexpression. Taken together, these findings demonstrated that AM was produced by synovial fibroblasts and macrophages in inflamed ST and that increased levels of AM may exert anti-inflammatory effects on synovial macrophages.
authors.affiliation: Department of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-ku Kitasato, Sagamihara City, Kanagawa 252-0374, Japan.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Takano
authors.affiliation: Department of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-ku Kitasato, Sagamihara City, Kanagawa 252-0374, Japan.
authors.forename: Kentaro
authors.identifier: 0000-0001-5148-914X
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Department of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-ku Kitasato, Sagamihara City, Kanagawa 252-0374, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyagi
authors.affiliation: Department of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-ku Kitasato, Sagamihara City, Kanagawa 252-0374, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Inoue
authors.affiliation: Department of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-ku Kitasato, Sagamihara City, Kanagawa 252-0374, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Aikawa
authors.affiliation: Department of Immunology, Kitasato University School of Medicine, 1-15-1 Minami-ku Kitasato, Sagamihara City, Kanagawa 252-0374, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Iwabuchi
authors.affiliation: Department of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-ku Kitasato, Sagamihara City, Kanagawa 252-0374, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Takaso
mesh_terms: D053607:Adrenomedullin / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D005347:Fibroblasts / Q000276:immunology; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics* / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D010329:Patella / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D058263:Receptor Activity-Modifying Protein 2 / Q000235:genetics; D058264:Receptor Activity-Modifying Protein 3 / Q000235:genetics; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013585:Synovitis / Q000235:genetics* / Q000276:immunology*
chemical_list: D053583:Interleukin-1beta; C545506:Ramp2 protein, mouse; C545507:Ramp3 protein, mouse; D058263:Receptor Activity-Modifying Protein 2; D058264:Receptor Activity-Modifying Protein 3; D053607:Adrenomedullin