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

Cvikl, Barbara; Lussi, Adrian; Moritz, Andreas; Sculean, Anton; Gruber, Reinhard (2015). Sterile-filtered saliva is a strong inducer of IL-6 and IL-8 in oral fibroblasts. Clinical oral investigations, 19(2), pp. 385-399. Springer 10.1007/s00784-014-1232-3

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > School of Dental Medicine > School of Dental Medicine, Restorative Dentistry, Research
04 Faculty of Medicine > School of Dental Medicine > Department of Preventive, Restorative and Pediatric Dentistry
04 Faculty of Medicine > School of Dental Medicine > Department of Periodontology
04 Faculty of Medicine > School of Dental Medicine > School of Dental Medicine, Periodontics Research

UniBE Contributor:

Cvikl, Barbara; Lussi, Adrian; Sculean, Anton and Gruber, Reinhard

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1432-6981

Publisher:

Springer

Language:

English

Submitter:

Eveline Carmen Schuler

Date Deposited:

03 Nov 2015 08:01

Last Modified:

25 Jan 2017 12:15

Publisher DOI:

10.1007/s00784-014-1232-3

PubMed ID:

25115993

Uncontrolled Keywords:

Saliva, Inflammation, Fibroblasts, Cytokines, NFκB, Microarray, Luminex technology

BORIS DOI:

10.7892/boris.72336

URI:

https://boris.unibe.ch/id/eprint/72336

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