S100A9-induced release of interleukin (IL)-6 and IL-8 through toll-like receptor 4 (TLR4) in human periodontal ligament cells |
| |
| Affiliation: | 1. Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing 100081, PR China;2. Department of Stomatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, PR China;3. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, PR China;4. Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, PR China;1. Institute of Biological and Environmental Sciences, University of Aberdeen, Tillydrone Avenue, Aberdeen, AB24 2TZ, UK;2. BioMar Ltd., Grangemouth Docks, Grangemouth FK3 8UL, UK;3. Institute of Biotechnology, National Cheng Kung University, Tainan 70101, Taiwan, ROC;1. Cellular and Molecular Immunology Laboratory, Department of Laboratory Medicine, School of Tropical Medicine, 108, C. R. Avenue, Kolkata, 700073 West Bengal, India;2. Department of Human Physiology, University of Calcutta, 92, APC Road, Kolkata 700009, India;3. Laboratory of Virology, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India;1. Division of Surgical Oncology, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA;2. Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA;3. Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA;4. Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA;5. Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA;6. UCLA AIDS Institute, Los Angeles, CA, USA;7. The Molecular Biology Institute, University of California, Los Angeles, CA, USA;1. School of Biological Sciences, University of Missouri—Kansas City, Kansas City, MO 64110, United States;2. Department of Biochemistry & Molecular Biophysics, Kansas State University, Manhattan, KS 66506, United States;1. Department of Pediatrics, Division of Pediatric Hematology/Oncology, University Hospitals Rainbow Babies & Children''s Hospital Center, The Angie Fowler Adolescent & Young Adult Cancer Institute, United States;2. The Case Comprehensive Cancer Center, Case Western Reserve University, United States;3. Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, United States;1. NBLI – Núcleo de Bioinformática do Laboratório de Imunogenética, Departamento de Genética, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, Building 43323, room 225, Brazil;2. Programa de Pós-Graduação em Genética e Biologia Molecular (PPGBM), Universidade Federal do Rio Grande do Sul (UFRGS), Rio Grande do Sul, Porto Alegre, Brazil;3. Department of Computer Science, Rice University, Houston, Texas, 77005, USA |
| |
| Abstract: | S100A8, S100A9, and calprotectin (the S100A8/S100A9 complex) are calcium-binding proteins that promote extracellular pro-inflammatory functions and may play an important role in periodontal disease. Both toll-like receptor 4 (TLR4) and the receptor for advanced glycation end-products (RAGE) are thought to be important receptors for S100A8, S100A9, and calprotectin, but the specific pathways in periodontal ligament (PDL) cells are not yet clear. Our study was designed to identify the specific receptors for S100A9 in human PDL cells. Additionally, we investigated the specific pathways that activate the secretion of pro-inflammatory cytokines interleukins (IL)-6 and IL-8 in PDL cells. The role of nuclear factor (NF)-κB, mitogen-activated protein kinase (MAPK) and reactive oxygen species (ROS) in S100A9-induced pro-inflammatory cytokines were investigated through western blot analysis, dichlorodihydrofluorescein diacetate (H2DCFDA) probe and the application of specific pathway inhibitors. Our results suggest that the S100A9-induced release of IL-6 and IL-8 from human PDL cells is dependent on TLR4, but not RAGE. We provide evidence that S100A9 promotes the secretion of IL-6 and IL-8 through different pathways. Specifically, S100A9 up-regulates the secretion of IL-6 from human PDL cells through NF-κB and p38 pathways and up-regulates the release of IL-8 from human PDL cells through the NF-κB, extracellular-regulated kinase (ERK) 1/2, c-Jun amino-terminal kinase (JNK) 1/2, and p38 signaling pathways. In addition, the release of both cytokines depends on ROS production. The release of both cytokines depends on ROS production. These results suggest that S100A9 promotes pro-inflammatory responses in PDL cells through the TLR4-mediated NF-κB and MAPK signaling pathways. |
| |
| Keywords: | S100A9 Pro-inflammatory effects PDL cells |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
