title: Allograft inflammatory factor-1 stimulates chemokine production and induces chemotaxis in human peripheral blood mononuclear cells.
abstract: Allograft inflammatory factor-1 (AIF-1) is expressed by macrophages, fibroblasts, endothelial cells and smooth muscle cells in immune-inflammatory disorders such as systemic sclerosis, rheumatoid arthritis and several vasculopathies. However, its molecular function is not fully understood. In this study, we examined gene expression profiles and induction of chemokines in monocytes treated with recombinant human AIF (rhAIF-1). Using the high-density oligonucleotide microarray technique, we compared mRNA expression profiles of rhAIF-1-stimulated CD14(+) peripheral blood mononuclear cells (CD14(+) PBMCs) derived from healthy volunteers. We demonstrated upregulation of genes for several CC chemokines such as CCL1, CCL2, CCL3, CCL7, and CCL20. Next, using ELISAs, we confirmed that rhAIF-1 promoted the secretion of CCL3/MIP-1α and IL-6 by CD14(+) PBMCs, whereas only small amounts of CCL1, CCL2/MCP-1, CCL7/MCP-3 and CCL20/MIP-3α were secreted. Conditioned media from rhAIF-1stimulated CD14(+) PBMCs resulted in migration of PBMCs. These findings suggest that AIF-1, which induced chemokines and enhanced chemotaxis of monocytes, may represent a molecular target for the therapy of immune-inflammatory disorders.
authors.affiliation: Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kadoya
authors.affiliation: Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Aihiro
authors.initials: A
authors.lastname: Yamamoto
authors.affiliation: Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Hamaguchi
authors.affiliation: Institute of Bio-Response Informatics, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Obayashi
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Katsura
authors.initials: K
authors.lastname: Mizushima
authors.affiliation: Department of Medical Biochemistry, Kobe Pharmaceutical University, Kobe, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Ohta
authors.affiliation: Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Rheumatic Diseases and Joint Function, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Seno
authors.affiliation: Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Oda
authors.affiliation: Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Fujiwara
authors.affiliation: Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Kohno
authors.affiliation: Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: kawahity@koto.kpu-m.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawahito
mesh_terms: D002135:Calcium-Binding Proteins; D054405:Chemokine CCL3 / Q000096:biosynthesis / Q000235:genetics; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008840:Microfilament Proteins; D009000:Monocytes / Q000276:immunology / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: C112986:AIF1 protein, human; C515429:CCL3 protein, human; D002135:Calcium-Binding Proteins; D054405:Chemokine CCL3; D019742:Chemokines, CC; D004268:DNA-Binding Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008840:Microfilament Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins
keywords: AIF-1; Allograft inflammatory factor-1; Chemotaxis; IL-6; MIP-1α