| Autor: |
Selimovic D; Institut National de la Santé et de la Recherche Médicale, University of Strasbourg, 67000 Strasbourg, France.; Department of Restorative Dentistry, Endodontology and Biomaterials, Faculty of Dentistry, University of Tours, 37000 Tours, France., Kharouf N; Institut National de la Santé et de la Recherche Médicale, University of Strasbourg, 67000 Strasbourg, France.; Department of Operative Dentistry and Endodontics, Dental Faculty, University of Strasbourg, 67000 Strasbourg, France., Carrouel F; Health, Systemic, Process, UR 4129 Research Unit, University Claude Bernard Lyon 1, University of Lyon, 69008 Lyon, France., Hassan SY; Department of Chemistry, Faculty of Science, Heinrich-Heine University Duesseldorf, 40225 Duesseldorf, Germany., Flanagan TW; Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, LA 70112, USA., Hassan SL; Department of Chemistry, Faculty of Science, Heinrich-Heine University Duesseldorf, 40225 Duesseldorf, Germany., Megahed M; Clinic of Dermatology, University Hospital of Aachen, 52074 Aachen, Germany., Haikel Y; Institut National de la Santé et de la Recherche Médicale, University of Strasbourg, 67000 Strasbourg, France.; Department of Operative Dentistry and Endodontics, Dental Faculty, University of Strasbourg, 67000 Strasbourg, France., Santourlidis S; Institute of Cell Therapeutics and Diagnostics, University Medical Center of Duesseldorf, 40225 Duesseldorf, Germany., Hassan M; Institut National de la Santé et de la Recherche Médicale, University of Strasbourg, 67000 Strasbourg, France.; Department of Operative Dentistry and Endodontics, Dental Faculty, University of Strasbourg, 67000 Strasbourg, France.; Research Laboratory of Surgery-Oncology, Department of Surgery, Tulane University School of Medicine, New Orleans, LA 70112, USA. |
| Abstrakt: |
The antimicrobial protein S100A15 belongs to the S100 family, which is differentially expressed in a variety of normal and pathological tissues. Although the function of S100A15 protein has been discussed in several studies, its induction and regulation in oral mucosa, so far, are largely unknown. In this study, we demonstrate that S100A15 is induced by the stimulation of oral mucosa with gram - or gram + bacterial pathogens, as well as with the purified membrane components, namely lipopolysaccharides (LPS) and lipoteichoic acid (LTA). The stimulation of the human gingival fibroblast (GF) and the human mouth epidermal carcinoma (KB) cell lines with either gram - or gram + bacterial pathogens or their purified membrane components (LPS and LTA) results in the activation of NF-κB, apoptosis-regulating kinase1 (ASK1), and MAP kinase signaling pathways including, c-Jun N-terminal kinase (JNK) and p38 together with their physiological substrates AP-1 and ATF-2, respectively. Inhibition of S100A15 by antibodies-mediated Toll-like receptor 4 (TLR4) or Toll-like receptor 2 (TLR2) neutralization reveals the induction of S100A15 protein by LPS/gram - bacterial pathogens to be TLR4- dependent mechanism, whereas induction by LTA/gram + bacterial pathogens to be TLR2- dependent mechanism. Pre-treatment of GF and KB cells with JNK (SP600125), p38 (SB-203580), or NF-κB (Bay11-7082) specific inhibitors further demonstrates the importance of JNK, p38 and NF-κB pathways in the regulation of gram - /gram + bacterial pathogen-induced S100A15 expression. Our data provide evidence that S100A15 is induced in cancer and non-cancer oral mucosa-derived cell lines by gram - /gram + bacterial pathogens and provide insight into the molecular mechanisms by which gram - and gram + bacterial pathogens induce S100A15 expression in the oral mucosa. |
