Independent thesis Advanced level (professional degree), 20 credits / 30 HE credits
The level of osteotropic cytokines is a crucial factor for alveolar bone loss in patients with periodontal disease. These cytokines,are produced by infiltrating immune cells as an inflammatory response. Besides their immunoregulatory function, certain osteotropic cytokines present in periodontitis can stimulate osteoclastogenes and alveolar bone resorption. Also resident cells, including gingival fibroblasts, produce these types of cytokines, a production which is regulated by different local inflammatory mediators. The role of systemic factors, such as hormones, in regulation of cytokine expression in gingival fibroblasts is, however, much less investigated. The aim of the present study was to investigate how vitamin D (1a,25-dihydroxyvitamin D3) affects the production of certain osteotropic cytokines in human gingival fibroblasts (HGF).
The fibroblasts were isolated from patients with clinically healthy gingiva. The evaluation of cytokine expression was made using RT-PCR after incubation of the fibroblasts in the presence or absence of 1a,25-Dihydroxyvitamin D3. Assessments of protein expression of cytokines and hormone receptors were performed using Western blot or ELISA.
In TNF-a stimulated HGFs, 1a,25-dihydroxyvitamin D3 caused a time- and concentration dependent decreased expression of IL-1β mRNA with no significant effect on the expression of IL-6 mRNA. 1a,25-dihydroxyvitamin D3 inhibited also the increased intracellular levels of pro-IL-1b in TNF-a stimulated cells. Western blot analysis demonstrated that HGF expressed vitamin D receptor protein as well as its dimerizing partner retinoid X receptor-a. These data show that vitamin D is a potent regulator of IL-1b in HGF which may help to explain the anti-inflammatory effect by vitamin D in vivo.