Aggregatibacter actinomycetemcomitans is the most important etiologic agent of aggressive periodontitis and can interact with endothelial cells. Monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) are chemokines, playing important roles in periodontal pathogenesis. In our current study, the effects of A. actinomycetemcomitans on the production of MCP-1 and IL-8 by human umbilical vein endothelial cells (HUVEC) were investigated. A. actinomycetemcomitans strongly induced the gene expression and protein release of both MCP-1 and IL-8 in a dose- and time-dependent manner. Dead A. actinomycetemcomitans cells were as effective as live bacteria in this induction. Treatment of HUVEC with cytochalasin D, an inhibitor of endocytosis, did not affect the mRNA up-regulation of MCP-1 and IL-8 by A. actinomycetemcomitans. However, genistein, an inhibitor of protein tyrosine kinases, substantially inhibited the MCP-1 and IL-8 production by A. actinomycetemcomitans, whereas pharmacological inhibition of each of three members of mitogen-activated protein (MAP) kinase family had little effect. Furthermore, gel shift assays showed that A. actinomycetemcomitans induces a biphasic activation (early at 1-2 h and late at 8-16 h) of nuclear factor-κB (NF-κB) and an early brief activation (0.5-2 h) of activator protein-1 (AP-1). Activation of canonical NF-κB pathway (IκB kinase activation and IκB-α degradation) was also demonstrated in these experiments. Although lipopolysaccharide from A. actinomycetemcomitans also induced NF-κB activation, this activation profile over time differed from that of live A. actinomycetemcomitans. These results suggest that the expression of MCP-1 and IL-8 is potently increased by A. actinomycetemcomitans in endothelial cells, and that the viability of A. actinomycetemcomitans and bacterial internalization are not required for this effect, whereas the activation of protein tyrosine kinase(s), NF-κB, and AP-1 appears to play important roles. The secretion of high levels of MCP-1 and IL-8 resulting from interactions of A. actinomycetemcomitans with endothelial cells may thus contribute to the pathogenesis of aggressive periodontitis.

In odontogenic osteolytic lesions, the mechanism involved in inflammation 때d osteolysis is still under debate. We investigated the role 。OL-l ~ -1 ß, -4, -6, -8, TNF- a in the expansion of the odontogenic cysts, by using 50 cases of excised odontogenic cysts. The degrees of inflammation were graded into 2 groups and immunohistochernical stainings were performed, The cytoplasrnic reaction in squamous epithelial cells, stromal cells and infIitrating inflammatory cells was examined. The relationship between the expressions of IL-1 q -1 ß, -4, -6, -8, π-JF- aand the degree of inflammation and the correlation among them were analyzed. 까1e 비Stilαγtic expressions of IL-l ~ IL-l ß and TNF-awere 66.6%, 66.6% and 4O.00Al respeαively and the epithelial exp~않sions of IL-4, -6, -8 were 32.00Al, 38.00Al and 24.00Al respeαively. IL-4, -6 and 용 were positively stained in plasma cells in 38.00Al, endothelial cells in 40.00/0 and neutrophils in 24. 00Al respectively. The expresssion rate of IL-4 in plasma cells and IL-8 in epithelium and neutrophils were inα얹sed in ca않s with marked inflammation. 까1e exp!1않sion rate of IL-1 ßin 피해ocytes and IL-4 in plasma cells were positively correlated with the expæssion of TNF-1 ain histiocytes. π1e expression rate of anti-inflammatory cytokine IL-4 in the epithelium were correlated with the expression of IL-6 in the epithelium and endothelial cells. A1though statistically insi.맑표ìcant， the expression rate of IL-6 were decreased in cases with marked inflammation and nega디vely correlated with IL-8, the proinflammatory cytokine, and the expressions of IL-4 and IL-6 in the epithelium can be considered as inhibiting the inflammatory reaction. These results suggest that the expressions of IL-4 and IL-6 suppress and IL-8 stimulates the inflammatory reaction in Odontogenic Cysts.