title: Sterile-filtered saliva is a strong inducer of IL-6 and IL-8 in oral fibroblasts.
abstract: OBJECTIVE
  Saliva has been implicated to support oral wound healing, a process that requires a transient inflammatory reaction. However, definitive proof that saliva can provoke an inflammatory response remained elusive.
  
  
  METHODS
  We investigated the ability of freshly harvested and sterile-filtered saliva to cause an inflammatory response of oral fibroblasts and epithelial cells. The expression of cytokines and chemokines was assessed by microarray, RT-PCR, immunoassays, and Luminex technology. The involvement of signaling pathways was determined by Western blot analysis and pharmacologic inhibitors.
  
  
  RESULTS
  We report that sterile-filtered whole saliva was a potent inducer of IL-6 and IL-8 in fibroblasts from the gingiva, the palate, and the periodontal ligament, but not of oral epithelial cells. This strong inflammatory response requires nuclear factor-kappa B and mitogen-activated protein kinase signaling. The pro-inflammatory capacity is heat stable and has a molecular weight of <40 kDa. Genome-wide microarrays and Luminex technology further revealed that saliva substantially increased expression of other inflammatory genes and various chemokines. To preclude that the observed pro-inflammatory activity is the result of oral bacteria, sterile-filtered parotid saliva, collected under almost aseptic conditions, was used and also increased IL-6 and IL-8 expression in gingiva fibroblasts. The inflammatory response was, furthermore, independent of MYD88, an adapter protein of the Toll-like receptor signaling pathway.
  
  
  CONCLUSIONS
  We conclude that saliva can provoke a robust inflammatory response in oral fibroblasts involving the classical nuclear factor-kappa B and mitogen-activated protein kinase signaling pathway.
  
  
  CONCLUSIONS
  Since fibroblasts but not epithelial cells show a strong inflammatory response, saliva may support the innate immunity of defect sites exposing the oral connective tissue.
authors.affiliation: Department of Preventive, Restorative and Pediatric Dentistry, School of Dental Medicine, University of Bern, Bern, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Cvikl
authors.forename: Adrian
authors.initials: A
authors.lastname: Lussi
authors.forename: Andreas
authors.initials: A
authors.lastname: Moritz
authors.forename: Anton
authors.initials: A
authors.lastname: Sculean
authors.forename: Reinhard
authors.initials: R
authors.lastname: Gruber
mesh_terms: D004203:Disinfection; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis*; D016906:Interleukin-9 / Q000096:biosynthesis*; D009055:Mouth / Q000166:cytology / Q000378:metabolism*; D012463:Saliva
chemical_list: D018836:Inflammation Mediators; D015850:Interleukin-6; D016906:Interleukin-9