Journal Article

The Pro-Apoptotic and Pro-Inflammatory Effects of Calprotectin on Human Periodontal Ligament Cells

Zhang, Xin, Meng, Huanxin, Jia, Lingfei, Wei, Shicheng, Zheng, Yunfei, Wang, Xian'e, Peng, Lei, Hou, Jianxia

2014

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Aggressive Periodontitis - genetics / Aggressive Periodontitis - metabolism / Aggressive Periodontitis - pathology / Antibiotics / Apoptosis / Apoptosis - drug effects / Arthritis / Biology and Life Sciences / Bleeding / Calgranulin A - biosynthesis / Calgranulin A - genetics / Calgranulin B - biosynthesis / Calgranulin B - genetics / Calgranulin B - pharmacology / Cancer therapies / Case-Control Studies / Comparative analysis / Connective Tissue Cells - cytology / Connective Tissue Cells - drug effects / Connective Tissue Cells - metabolism / Cyclooxygenase 2 - genetics / Cyclooxygenase 2 - metabolism / Cyclooxygenase-2 / Cystic fibrosis / Cytokines / Disease / Female / Fibrosis / Gene Expression / Gingival Crevicular Fluid - chemistry / Gum disease / Hospitals / Humans / Inflammation / Inflammatory diseases / Inflammatory response / Interleukin 6 / Interleukin 8 / Interleukin-6 - genetics / Interleukin-6 - metabolism / Interleukin-8 - genetics / Interleukin-8 - metabolism / Kinases / Leukocyte L1 Antigen Complex - biosynthesis / Leukocyte L1 Antigen Complex - genetics / Leukocyte L1 Antigen Complex - pharmacology / Ligaments / Male / Maxillofacial surgery / Medicine and Health Sciences / Neutrophils / NF-kappa B - antagonists & inhibitors / NF-kappa B - genetics / NF-kappa B - metabolism / NF-κB protein / Nuclear transport / Patients / Periodontal ligament / Periodontal Ligament - cytology / Periodontal Ligament - drug effects / Periodontal Ligament - metabolism / Periodontitis / Primary Cell Culture / Proline - analogs & derivatives / Proline - pharmacology / Proteins / Recombinant Proteins - biosynthesis / Recombinant Proteins - genetics / Recombinant Proteins - pharmacology / Rheumatoid arthritis / Rheumatoid factor / Surgery / Thiocarbamates - pharmacology / Translocation / Tumor Necrosis Factor-alpha - genetics / Tumor Necrosis Factor-alpha - metabolism / Tumor necrosis factor-α