title: Paneth cells regulate both chemotaxis of immature dendritic cells and cytokine production from epithelial cells.
abstract: Paneth cells in the small intestine are able to sense luminal bacteria and secrete granules that contain antibacterial peptides.  Human defensin (HD)-5 and -6 are antimicrobial peptides found in human Paneth cell granules, and are major bactericidal components.  We investigated whether any constituents in the Paneth cell secretions showed chemotactic activity or stimulated cytokine secretion from intestinal epithelial cells, and assessed to what extent HD-5 and -6 were responsible for these activities.  The secretions from human Paneth cells and recombinant HD-5 and -6 were evaluated to elucidate their effects on the chemotaxis of dendritic cells (DCs) in a migration assay.  The Paneth cell secretions were chemotactic for immature DCs at concentrations ranging from 10 to 1,000 µg/ml.  HD-6 was active at 100 ng/ml, but HD-5 was not.  Next, the stimulation of cytokine production by the T84 intestinal cell line was assessed using ELISA and/or an antibody array.  The secretions more strongly stimulated interleukin (IL)-8 production than did the defensin peptides, and induced production of various cytokines by the antibody array.  The secretions were also analyzed by high performance liquid chromatography (HPLC) and mass spectrometry (MS) in order to determine the components.  A large number of molecules was found in the secretions, and HD-5 was identified as an immature propeptide.  In conclusion, some constituents other than defensin in human Paneth cell secretions activated the migration of DCs and induced the production of inflammatory cytokines.  Therefore, Paneth cells may play a role in the innate immunity associated with adaptive immune responses.
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, Japan. dr-ito@asahikawa-med.ac.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ito
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanabe
authors.forename: Tokiyoshi
authors.initials: T
authors.lastname: Ayabe
authors.forename: Chisato
authors.initials: C
authors.lastname: Ishikawa
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Inaba
authors.forename: Atsuo
authors.initials: A
authors.lastname: Maemoto
authors.forename: Toru
authors.initials: T
authors.lastname: Kono
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ashida
authors.forename: Mikihiro
authors.initials: M
authors.lastname: Fujiya
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kohgo
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D004359:Drug Therapy, Combination; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D007419:Intestinal Secretions / Q000737:chemistry / Q000378:metabolism; D019879:Paneth Cells / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins; D023084:alpha-Defensins / Q000494:pharmacology; D023083:beta-Defensins / Q000494:pharmacology
chemical_list: D016207:Cytokines; D011994:Recombinant Proteins; D023084:alpha-Defensins; D023083:beta-Defensins