title: Toll-like receptor activation and mechanical force stimulation promote the secretion of matrix metalloproteinases 1, 3 and 10 of human periodontal fibroblasts via p38, JNK and NF-kB.
abstract: Matrix metalloproteinases (MMPs) are known to play a key role during orthodontic treatment leading to periodontal remodelling and tooth movement. MMPs may be induced by mechanical forces. However, the role played by toll-like receptors (TLRs) in modulating the effects of the mechanical force on periodontal fibroblasts is not known. To investigate the interaction between mechanical force and TLR stimulation, primary cultures of human periodontal fibroblasts were submitted to centrifugation in the presence of LPS and Pam3Cys, which are known TLR-4 and TLR-2 ligands, respectively. The expression of MMP-1, -2, -3, -8, -9, -10 and -13; TIMP (Tissue Inhibitor of Metalloproteinases) -1, -2 and -4; TNF-α (Tumour Necrosis Factor alpha); IL-1β (Interleukin 1 beta); ERK 1/2 (Extracellular Signal-Regulated Kinase 1/2); p38; JNK (c-jun N-terminal Kinase); IRAK1 (Interleukin-1 Receptor-Associated Kinase); and NF-κB (Nuclear Factor kappa B) were measured by antibody array, ELISA and immunoblotting methods. The activation of TLRs associated with centrifugation induced an increase in the secretion of MMPs 1, 3 and 10, with no increase in TNF-α or IL-1β. An increase in the phosphorylation of the MAP kinases p38 and JNK and the transcription factor NF-κB, without an increase in TIMPs was also observed. These findings suggest that the secretion of MMPs by cultured periodontal fibroblasts that is induced by combined TLR activation and mechanical force stimulation is regulated via the p38, JNK and NF-κB pathways. The increased secretion of MMPs by TLR activation may be an important factor that should be considered during orthodontic treatment.
authors: Department of Pathology, School of Medicine, Universidade Federal de Minas Gerais (UFMG), 30130-100 Belo Horizonte, MG, Brazil.
authors: Rodolfo Assis
authors: RA
authors: Lisboa
authors: Marcus Vinícius
authors: MV
authors: Andrade
authors: José Renan
authors: JR
authors: Cunha-Melo
mesh_terms: D001696:Biomechanical Phenomena; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002498:Centrifugation; D003603:Cytotoxins / Q000494:pharmacology; D005347:Fibroblasts / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008074:Lipoproteins / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D020781:Matrix Metalloproteinase 1 / Q000032:analysis / Q000378:metabolism*; D053506:Matrix Metalloproteinase 10 / Q000032:analysis / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000032:analysis / Q000378:metabolism*; D016328:NF-kappa B / Q000502:physiology*; D010513:Periodontal Ligament / Q000166:cytology* / Q000201:enzymology; D013314:Stress, Mechanical; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis; D051195:Toll-Like Receptor 2 / Q000187:drug effects / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000187:drug effects / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D003603:Cytotoxins; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008074:Lipoproteins; D048670:MAP Kinase Kinase 4; D020781:Matrix Metalloproteinase 1; D053506:Matrix Metalloproteinase 10; D019278:Matrix Metalloproteinase 3; D016328:NF-kappa B; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000097792:Tissue Inhibitor of Metalloproteinase-4; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C061108:N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine; C511768:MMP3 protein, human; C511770:MMP10 protein, human; C522360:MMP1 protein, human