title: Up-regulation of TLR2 and TLR4 in high mobility group Box1-stimulated macrophages in pulpitis patients.
abstract: OBJECTIVE
  High Mobility Group Box1 (HMGB1) is a nonhistone, DNA-binding protein that serves a crucial role in regulating gene transcription and is involved in a variety of proinflammatory, extracellular activities. The aim of this study was to explore whether HMGB1 stimulation can up-regulate the expression of Toll-like Receptor 2 (TLR2) and Toll-like Receptor 4 (TLR4) on macrophages from pulpitis and to clarify the subsequent events involving Th17 cells and Th17 cell-associated cytokine changes.
  
  
  METHODS
  Having prepared dental pulp tissues of pulpitis and healthy controls, macrophage were isolated and cultured. Macrophages were thereafter stimulated by HMGB1 time course. RT-QPCR, flowcytometer, immunofluorescence, Western blotting, and ELISA techniques were used in the present research.
  
  
  RESULTS
  Our results showed that the expression of TLR2 and TLR4 on macrophages stimulated with HMGB1 increased in pulpitis compared with controls (macrophages without HMGB1 stimulation) with a statistical significance (P<0.001). In addition, the levels of IL-17, IL-23, and IL-6 in supernatants from cultured macrophages stimulated with HMGB1 from pulpitis increased, and NF-kB, the downstream target of TLR2 and TLR4, also showed a marked elevation after macrophages' stimulation by HMGB1.
  
  
  CONCLUSIONS
  The evidence from the present study suggests that the enhanced TLR2 and TLR4 pathways and Th17 cell polarization may be due to HMGB1 stimulation in pulpitis.
authors.affiliation: Neurosciences Research Center, Tabriz University of Medical Science, Tabriz, Iran.
authors.forename: Javad
authors.initials: J
authors.lastname: Mahmoudi
authors.affiliation: Neurosciences Research Center, Tabriz University of Medical Science, Tabriz, Iran.
authors.forename: Babak
authors.initials: B
authors.lastname: Sabermarouf
authors.affiliation: Immunology Research Center, Tabriz University of Medical Science, Tabriz, Iran.
authors.forename: Behzad
authors.initials: B
authors.lastname: Baradaran
authors.affiliation: Immunology Research Center, Tabriz University of Medical Science, Tabriz, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Sadat-Hatamnezhad
authors.affiliation: Department of Immunology, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
authors.forename: Siamak Sandoghchian
authors.initials: SS
authors.lastname: Shotorbani
keywords: HMGB1; Pulpitis; TLR2; TLR4