title: S100A9-induced release of interleukin (IL)-6 and IL-8 through toll-like receptor 4 (TLR4) in human periodontal ligament cells.
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.
authors.affiliation: Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing 100081, PR China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing 100081, PR China; Department of Stomatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing 100081, PR China; Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, PR China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing 100081, PR China; Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Peng
authors.affiliation: Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing 100081, PR China. Electronic address: jxhou@163.com.
authors.forename: Jianxia
authors.initials: J
authors.lastname: Hou
authors.affiliation: Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing 100081, PR China. Electronic address: kqhxmeng@bjmu.edu.cn.
authors.forename: Huanxin
authors.initials: H
authors.lastname: Meng
mesh_terms: D000293:Adolescent; D000328:Adult; D040502:Calgranulin B / Q000378:metabolism*; D005260:Female; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D055815:Young Adult
chemical_list: C000593871:AGER protein, human; D040502:Calgranulin B; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: PDL cells; Pro-inflammatory effects; S100A9