Sterile-filtered saliva is a strong inducer of IL-6 and IL-8 in oral fibroblasts
Authors
Barbara Cvikl & Adrian Lussi & Andreas Moritz & Anton Sculean & Reinhard Gruber
Institution
Uni Bern
Country
Switzerland
Year
2014
Journal
Clin Oral Invest
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