High glucose induces inflammatory cytokine through protein kinase C-induced toll-like receptor 2 pathway in gingival fibroblasts

Toll-like receptors (TLRs) play a key role in innate immune response and inflammation, especially in peridontitis. Meanwhile, hyperglycemia can induce inflammation in diabetes complications. However, the activity of TLRs in periodontitis complicated with hyperglycemia is still unclear. In the present study, high glucose (25 mmol/l) significantly induced TLR2 expression in gingival fibroblasts (p < 0.05). Also, high glucose increased nuclear factor kappa B (NF-kappa B) p65 nuclear activity, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) levels. Protein kinase C (PKC)-alpha and delta knockdown with siRNA significantly decreased TLR2 and NF-kappa B p65 expression (p < 0.05), whereas inhibition of pKC-beta had no effect on TLR2 and NF-kappa B p65 under high glucose (p < 0.05). Additional studies revealed that TLR2 knockdown significantly abrogated high-glucose-induced NF-kappa B expression and inflammatory cytokine secretion. Collectively, these data suggest that high glucose stimulates TNF-alpha and IL-1 beta secretion via inducing TLR2 through PKC-alpha and PKC-delta in human gingival fibroblasts. (C) 2012 Elsevier Inc. All rights reserved.