Peptidoglycan Induces the Production of Interleukin-8 via Calcium Signaling in Human Gingival Epithelium

The etiology of periodontal disease is multifactorial. Exogenous stimuli such as bacterial pathogens can interact with toll-like receptorsto activate intracellular calcium signalingin gingivalepithelium and other tissues. The triggering of calcium signalinginduces the secretion of pro-inflammatory cytokines such as interleukin-8 as part of the inflammatory response; however, the exact mechanism of calcium signalinginduced by bacterial toxins when gingivalepithelial cells are exposed to pathogens is unclear. Here, we investigate calcium signalinginduced by bacteria and expression of inflammatory cytokines in human gingivalepithelial cells. We found that peptidoglycan, a constituent of gram-positive bacteria and an agonist of toll-like receptor2, increases intracellular calciumin a concentration-dependent manner. Peptidoglycan-induced calcium signalingwas abolished by treatment with blockers of phospholipase C({"type":" entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075","term_text":"U73122"}}U73122), inositol 1,4,5-trisphosphate receptors, indicating the release of calciumfrom intracellular calciumstores. Peptidoglycan-mediated interleukin-8 expression was blocked by {"type":" entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075","term_text":"U73122"}}U73122 and 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester). Moreover, interleukin-8 expression was induced by thapsigargin, a selective inhibitor of the sarco/endoplasmic reticulum calcium ATPase, when thapsigarginwas treated alone or co-treated with peptidoglycan. These results suggest that the gram-positive bacterial toxin peptidoglycaninduces calcium signalingvia the phospholipase C/inositol 1,4,5-trisphosphate pathway, and that increased interleukin-8 expression is mediated by intracellular calciumlevels in human gingivalepithelial cells.