Zinc modulates IL-1b-stimulated chemokine secretion in human gingival fibroblasts.

Objectives: Zinc (Zn) is an essential micronutrient involved in a vast array of cellular functions. There is well established evidence that sub-clinical Zn deficiency is important with respect to immune function. Despite the evident link between immune response and dietary intake of Zn, the precise mechanisms by which cellular Zn influences immune function are unclear. The effect of Zn deficiency on the pathogenesis of periodontal disease has not been examined; however preliminary experiments in rat models indicate Zn deficiency as a risk factor for periodontal disease.
Objective: to investigate whether Zn availability could modulate chemokine expression by human gingival fibroblasts (HGFs).
Methods: HGFs were cultured in serum free media (depleted) or media containing 20 µM (physiological) or 100 µM (supra-physiological) extracellular ZnCl₂ for 2 h prior to stimulation with 1 ng/ml IL-1β for a further 24h. Cytokine levels were measured using a cytokine protein array (Proteome Profiler, R&D Systems). Confirmation of results was carried out for IL-8 using a Human CXCL8/IL-8 DuoSet (R&D systems) ELISA kit.
Results: Stimulation of HGFs with IL-1β alone (Zn-depleted medium) resulted in a 5-fold increase in expression of CXCL1, IL-8 and MCP-1 compared with IL-1b stimulated HGF cells under physiological Zn concentrations (20 µM). However, in the presence of supra-physiological Zn concentrations (100 µM), IL-1b stimulated CXCL1, IL-8 and MCP-1 were at levels similar to those manifested in Zn depleted cells and these cultures exhibited a wider range of cytokine expression (IL-6, CXCL5, CXCL10, and CCL20) compared with other conditions. Quantitation of IL-8 demonstrated a significant increase in IL-1b stimulated cells in Zn-depleted and 100 µM Zn-supplemented media compared with cells exposed to 20 µM Zn (Table 1).
Conclusions: This preliminary data shows that Zn has a biphasic effect on chemokine secretion on HGF cells suggestive of a molecular role for Zn in periodontal disease. Further research investigating the mechanisms through which Zn is acting is necessary.