Expression of BDNF and TrkB in Gingival Inflammation

Abstract

The gingival epithelium is a physiologically important interface between the bacterially colonized gingival sulcus and periodontal soft and mineralized connective tissues which requires protection from exposure to bacteria and their products. Gingival inflammation results from the coordinated activation of cascades of signaling pathways initiated by growth factors and their receptors. Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, belong to the neurotrophin family of growth factors and mediate vital physiological functions in the brain, and they are expressed in a wide variety of non-neuronal tissues. Aberrant neurotrophin signaling underlies the pathogenesis of several inflammatory conditions, yet little is known about the role of neurotrophins in the gingival inflammation. To fill this gap in knowledge, we analyzed the patterns of BDNF and TrkB expression in the inflamed tissues of human and in experimental rat periodontitis tissues. Gingival tissues from patients with periodontitis demonstrated greater levels of BDNF and TrkB expression than the tissues from healthy individuals, while an in vivo rat study showed increased expression of BDNF and TrkB in experimental rat periodontitis tissues. Interleukin-1β(IL-1β), a pro-inflammatory cytokine, elevated the expression of BDNF and TrkB mRNAs in human gingival fibroblast (HGF) and human gingival epithelial (HGE) cells. Inducible NOS (iNOS) mRNA expression was elevated in HGF cells that were stimulated by IL-1β. Also, IL-1β stimulated protein expression of BDNF and iNOS in HGF cells. ELISA confirmed that the expression of BDNF by HGF was upregulated in the presence of IL-1β. Addition of S-Methylisothiourea Sulphate (SMT), a specific inhibitor of iNOS, profoundly reduced the production of BDNF in HGF. Together, these results support a role for BDNF as a new modulator of gingival inflammation. Gingival fibroblast cells within inflammatory environment can significantly increase the production of neurotrophic factors, which may be involved with the anti-inflammatory mechanisms.