title: Secretory leukocyte protease inhibitor inhibits expression of polymeric immunoglobulin receptor via the NF-κB signaling pathway.
abstract: Polymeric immunoglobulin receptor (pIgR) plays an important role in mucosal immune systems. Secretory immunoglobulin A, composed of secretory component of pIgR and a dimeric form of immunoglobulin A, is secreted on mucosal surfaces and serves as a biological defense factor. pIgR gene expression is reportedly induced by activation of the transcription factor nuclear factor (NF)-κB. On the other hand, secretory leukocyte protease inhibitor (SLPI) is a glycoprotein that functions as a serine protease inhibitor. In alveolar epithelial cells, SLPI increases the level of IκBβ, which indicates that it is an inhibitor of NF-κB at the protein level. Taken together, SLPI may regulate pIgR expression; however, the specific mechanism by which this occurs is unclear. Therefore, the aim of this study was to elucidatethe influence of SLPI on pIgR expression.SLPI and pIgR localized in goblet cells and ciliated epithelial cells of the gastrointestinal tract, respectively. No cells were detected in which SLPI and pIgR were co-expressed. In addition, recombinant human SLPI stimulation of an epithelial cell line (HT-29) decreased the pIgR expression. The pIgR expression was also higher in SLPI-deficient Ca9-22 cells than in wild-type Ca9-22 cells. Furthermore, a luciferase assay using a NF-κB reporter plasmid and real-time RT-PCR analysis indicated that when SLPI was present, the transcriptional activity of NF-κB protein was suppressed, which was accompanied by anincrease in the protein, but not the mRNA,expression of IκBβ. These results demonstrate that SLPI down-regulates pIgR expression through the NF-κB signaling pathway by inhibiting degradation of IκBβ protein.
authors.affiliation: Department of Pathology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Mikami
authors.affiliation: Department of Pathology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwase
authors.affiliation: Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi, 321-0293, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Komiyama
authors.affiliation: Department of Pathology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Maxillofacial Surgery, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
authors.forename: Hidero
authors.initials: H
authors.lastname: Oki
authors.affiliation: Department of Pathology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan. Electronic address: komiyama.kazuo@nihon-u.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Komiyama
mesh_terms: D041981:Gastrointestinal Tract / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D019073:HT29 Cells; D006801:Humans; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019056:Receptors, Polymeric Immunoglobulin / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012469:Salivary Glands / Q000378:metabolism / Q000473:pathology; D012635:Secretory Component / Q000378:metabolism; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B; D012333:RNA, Messenger; D019056:Receptors, Polymeric Immunoglobulin; D011994:Recombinant Proteins; C506814:SLPI protein, human; D012635:Secretory Component; D053481:Secretory Leukocyte Peptidase Inhibitor
keywords: Epithelial cells; NF-κB; SLPI; pIgR