Clinical Oral Investigations

, Volume 19, Issue 2, pp 385–399

Sterile-filtered saliva is a strong inducer of IL-6 and IL-8 in oral fibroblasts

  • Barbara Cvikl
  • Adrian Lussi
  • Andreas Moritz
  • Anton Sculean
  • Reinhard Gruber
Original Article

Abstract

Objectives

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.

Materials and 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.

Clinical relevance

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.

Keywords

Saliva Inflammation Fibroblasts Cytokines NFκB Microarray Luminex technology 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Barbara Cvikl
    • 1
    • 2
    • 3
  • Adrian Lussi
    • 1
  • Andreas Moritz
    • 3
  • Anton Sculean
    • 4
  • Reinhard Gruber
    • 1
    • 2
    • 4
  1. 1.Department of Preventive, Restorative and Pediatric Dentistry, School of Dental MedicineUniversity of BernBernSwitzerland
  2. 2.Laboratory of Oral Cell Biology, School of Dental MedicineUniversity of BernBernSwitzerland
  3. 3.Department of Conservative Dentistry and PeriodontologyMedical University of ViennaViennaAustria
  4. 4.Department of Periodontology, School of Dental MedicineUniversity of BernBernSwitzerland

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