title: Secretion of inflammatory factors from chondrocytes by layilin signaling.
abstract: Layilin (LAYN) is thought to be involved in reorganization of cytoskeleton structures, interacting with merlin, radixin, and talin. Also, LAYN is known to be one of the receptors for hyaluronic acid (HA). In rheumatoid arthritis (RA), inflammatory cytokines like tumor necrosis factor α (TNF-α) have been known to play pathological roles. HA with low molecular weight is speculated to exacerbate inflammation in RA. In this context, differences of quantity and functions of HA receptors would affect the severity of inflammation in RA. Chondrocytes, which play critical roles in maintaining articular cartilage and are affected in RA, express at least kinds of HA receptors like CD44 and LAYN. However, roles and regulation of LAYN in articular chondrocytes have been poorly understood. To clarify regulation of LAYN in chondrocytes, we here investigated whether TNF-α affected expression levels of LAYN in human articular chondrocytes. Next, to clarify LAYN-specific roles in chondrocytes, we investigated whether binding of antibodies to the extracellular domain of LAYN affected secretion of inflammatory cytokines using a chondrosarcoma cell line. As a result, we found that TNF-α up-regulated expression levels of LAYN in the chondrocytes. Further, the LAYN signaling was found to enhance secretion of inflammatory factors, IL-8 and complement5 (C5)/C5a, from the cells. Our results indicate that LAYN would be involved in the enhancement of inflammation and degradation of cartilage in joint diseases such as RA and OA.
authors.affiliation: Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, Kanagawa 216-8511, Japan. Electronic address: ysmwk987@yahoo.co.jp.
authors.forename: Kota
authors.initials: K
authors.lastname: Asano
authors.affiliation: Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, Kanagawa 216-8511, Japan. Electronic address: m-ari@marianna-u.ac.jp.
authors.forename: Mitsumi
authors.initials: M
authors.lastname: Arito
authors.affiliation: Disease Biomarker Analysis and Molecular Regulation, St. Marianna University Graduate School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, Kanagawa 216-8511, Japan. Electronic address: manae@marianna-u.ac.jp.
authors.forename: Manae S
authors.initials: MS
authors.lastname: Kurokawa
authors.affiliation: Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, Kanagawa 216-8511, Japan. Electronic address: omoteyama@marianna-u.ac.jp.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Omoteyama
authors.affiliation: Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, Kanagawa 216-8511, Japan. Electronic address: k2oka@marianna-u.ac.jp.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, Kanagawa 216-8511, Japan. Electronic address: n2sue@marianna-u.ac.jp.
authors.forename: Naoya
authors.initials: N
authors.lastname: Suematsu
authors.affiliation: Institute of Medical Science, St. Marianna University Graduate School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, Kanagawa 216-8512, Japan. Electronic address: yudo@marianna-u.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yudoh
authors.affiliation: Department of Orthopedic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan. Electronic address: nakamura@nms.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Department of Orthopaedic Surgery, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, Kanagawa 216-8511, Japan. Electronic address: mbortho7@marianna-u.ac.jp.
authors.forename: Moroe
authors.initials: M
authors.lastname: Beppu
authors.affiliation: Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, Kanagawa 216-8511, Japan. Electronic address: t3kato@marianna-u.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kato
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism*; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D017931:DNA Primers; D018836:Inflammation Mediators; C546934:LAYN protein, human; D037181:Lectins, C-Type
keywords: Chondrocytes; Complement5; Inflammation; Layilin; Rheumatoid arthritis; TNF-α