title: The pro-apoptotic and pro-inflammatory effects of calprotectin on human periodontal ligament cells.
abstract: Calprotectin, a heterodimer of S100A8 and S100A9 subunits, is associated with inflammatory disorders such as rheumatoid arthritis and cystic fibrosis. Although calprotectin levels are increased significantly in the gingival crevicular fluid (GCF) of periodontitis patients, its effects on periodontal ligament cells (PDLCs) remain largely unknown. The aim of this study was to evaluate calprotectin levels in the GCF of generalized aggressive periodontitis (AgP) patients and to investigate the effects of recombinant human calprotectin (rhS100A8/A9) and its subunits (rhS100A8 and rhS100A9) in PDLCs. Both the concentration and amount of crevicular calprotectin were significantly higher in the AgP group compared with healthy controls. In addition, the GCF calprotectin levels were correlated positively with clinical periodontal parameters including bleeding index, probing depth, and clinical attachment loss. rhS100A8/A9 promoted cell apoptosis, whereas rhS100A8 and rhS100A9 individually exerted little effect on apoptosis in PDLCs. rhS100A9 and rhS100A8/A9 increased the activation of nuclear factor-κB (NF-κB) by promoting the nuclear translocation of p65 in PDLCs, subsequently inducing expression of the pro-inflammatory cytokines IL-6, IL-8, TNFα, and COX2. Treatment with an NF-κB inhibitor partially reversed the rhS100A9- and rhS100A8/A9-induced upregulation of the pro-inflammatory cytokines. rhS100A9, and not rhS100A8, was mainly responsible for the pro-inflammatory role of calprotectin. Collectively, our results suggest that calprotectin promotes apoptosis and the inflammatory response in PDLCs via rhS100A9. These findings might help identify novel treatments for periodontitis.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, P.R. China; Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, P.R. China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, P.R. China.
authors.forename: Jianxia
authors.initials: J
authors.lastname: Hou
authors.affiliation: Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Beijing, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Peng
authors.affiliation: Department of Stomatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, P.R. China; Laboratory of Molecular Biology, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Lingfei
authors.initials: L
authors.lastname: Jia
authors.affiliation: Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, P.R. China.
authors.forename: Xian'e
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, P.R. China.
authors.forename: Shicheng
authors.initials: S
authors.lastname: Wei
authors.affiliation: Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, P.R. China.
authors.forename: Huanxin
authors.initials: H
authors.lastname: Meng
mesh_terms: D000328:Adult; D010520:Aggressive Periodontitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D040501:Calgranulin A / Q000096:biosynthesis / Q000235:genetics; D040502:Calgranulin B / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D016022:Case-Control Studies; D003239:Connective Tissue Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005883:Gingival Crevicular Fluid / Q000737:chemistry; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D039841:Leukocyte L1 Antigen Complex / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D061251:Primary Cell Culture; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D039841:Leukocyte L1 Antigen Complex; D016328:NF-kappa B; D011994:Recombinant Proteins; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C066229:prolinedithiocarbamate; D011392:Proline; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human