title: Levocetrizine has anti-inflammatory effects against Toll-like receptor (TLR)3 through the inhibition of Toll-IL-1 receptor (TIR)-domain-containing adapter inducing IFN-beta (TRIF) and receptor-interacting protein (RIP).
abstract: OBJECTIVE
  To investigate the anti-inflammatory effect of levocetrizine (LCEZ) on the intracellular adhesion molecule-1 (ICAM-1) in human nasal epithelial cells stimulated by TLR3 and further analyze the anti-inflammatory mechanism of LCEZ in the MyD88-independent pathway before NF-κB is activated.
  
  
  METHODS
  A primary culture of human nasal epithelial cells (HNECs) was generated from nasal polyps. After stimulation of epithelial cells with LTA, double-stranded RNA (dsRNA), and LPS, reverse transcription-polymerase chain reaction (RT-PCR) was performed at 1, 6, and 24 h to clarify the optimal stimulation of ICAM-1 in HNECs. To investigate the anti-inflammatory effects of LCEZ, HNECs were pretreated with three different concentrations of LCEZ (500, 50, and 5 nM) for 2 h. HNECs were washed and then stimulated with dsRNA. At 1, 6, and 24 h after stimulation, the level of ICAM-1 was measured by RT-PCR and ELISA. Western blots for TRIF and RIP were performed.
  
  
  RESULTS
  The level of ICAM-1 was significantly elevated by dsRNA. Pretreatment with LCEZ decreased the secretion of ICAM-1, which was observed in RT-PCR and Western blots but not in ELISA analyses. The expression of TRIF and RIP, measured by Western blot, was decreased by pretreatment with LCEZ.
  
  
  CONCLUSIONS
  The activation of HNECs by TLRs (especially TLR3) could trigger an inflammatory process, which might be inhibited by LCEZ through the suppression of TRIF and RIP proteins.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Chan-Soon
authors.initials: CS
authors.lastname: Park
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Cho
authors.forename: Jun-Myung
authors.initials: JM
authors.lastname: Kang
authors.forename: Byung-Kook
authors.initials: BK
authors.lastname: Kim
authors.forename: Min-Ah
authors.initials: MA
authors.lastname: Han
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000037:antagonists & inhibitors*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D017332:Cetirizine / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D009297:Nasal Mucosa / Q000187:drug effects / Q000473:pathology; D009298:Nasal Polyps / Q000473:pathology; D012330:RNA, Double-Stranded / Q000494:pharmacology; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013682:Teichoic Acids / Q000494:pharmacology; D051196:Toll-Like Receptor 3 / Q000037:antagonists & inhibitors*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D012330:RNA, Double-Stranded; C470409:TICAM1 protein, human; C495344:TLR3 protein, human; D013682:Teichoic Acids; D051196:Toll-Like Receptor 3; D018799:Intercellular Adhesion Molecule-1; C009900:lipoteichoic acid; C472067:levocetirizine; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D017332:Cetirizine