Tea Polyphenols Attenuate TNF-α-induced Epithelial Barrier Breakdown and Inflammatory Response
Objectives: Objectives: Tea, an aqueous aromatic infusion of the leaves of the Camellia sinensis plant, has a high polyphenol content. While green tea contains mainly catechins such as epigallocatechin-3-gallate (EGCG), black tea is characterized by the presence of theaflavins. Acting as a pro-inflammatory cytokine that activates the endogenous inflammatory cascade and as a highly potent inducer of epithelial tight junction (TJ) disruption, TNF-α plays a key role in periodontitis. In the present study, we first investigated the protective effect of green and black tea polyphenols on the gingival epithelial barrier dysfunction induced by TNF-α, and secondly the ability of tea compounds to attenuate TNF-α-mediated activation of the host inflammatory response. Methods: Methods: The effect of tea polyphenols against TNF-α-induced keratinocyte barrier disruption was evaluated by determination of transepithelial electrical resistance and transport of FITC-dextran. The localization of TJ proteins in keratinocytes treated with TNF-α and tea compounds was visualized by immunofluorescence microscopy. The anti-inflammatory properties of tea polyphenols were investigated by evaluating their effects on NF-κB activation in monocytes as well as on the secretion of pro-inflammatory cytokines (IL-1β) by macrophages and of chemokine (IL-8) by epithelial cells. Results: Results: A protective effect of tea polyphenols against the TNF-α-mediated breakdown of keratinocyte integrity was demonstrated. By immunofluorescence, it was found that a treatment of keratinocytes with tea polyphenols markedly prevented the morphological changes of TJ proteins such as ZO-1 and occludin compared to cells exposed only with TNF-α. Moreover, tea polyphenols time-dependently decreased the paracellular flux in TNF-α-treated keratinocytes. Lastly, compounds inhibited the activation of NF-κB and reduced the secretion of pro-inflammatory cytokines IL-1β and IL-8 by host cells. Conclusions: Conclusion: The ability of tea polyphenols to attenuate the gingival epithelial barrier dysfunction induced by TNF-α and to exert anti-inflammatory properties suggests that they may represent promising preventive or therapeutic agents against periodontal disease