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It is well known that proinflammatory cytokines produced by host cells play an important role in periodontal tissue destruction. However, the localization of the cytokines in in vivo periodontal tissues during development of periodontal disease has not been determined. Immunohistochemical expression of proinflammatory cytokines including IL-1??, IL-1??, and TNF-?? was examined at 1 and 3??h, and 1, 2, 3, and 7??days after topical application of lipopolysaccharide (LPS; 5??mg/ml in physiological saline) from E. coli into the rat molar gingival sulcus. In the normal periodontal tissues, a small number of cytokine-positive epithelial cells were seen in the junctional epithelium (JE), oral sulcular and oral gingival epithelium, in addition to macrophages infiltrating in the subjunctional epithelial area and osteoblasts lining the alveolar bone surface. Epithelial remnants of Malassez existing throughout periodontal ligament were intensely positive for IL-1?? but negative for the other two cytokines. At 3??h after the LPS treatment, almost all cells in the JE were strongly positive for the cytokines examined. In addition, several cytokine-positive cells, including neutrophils, macrophages, and fibroblasts, were seen in the subjunctional epithelial connective tissue. At day??2, expression of the cytokines in the JE gradually decreased, while cytokine-positive cells in the connective tissue increased in number. Positive staining of the cytokines was seen in osteoclasts and preosteoclasts which appeared along the alveolar bone margin in this period. The number of cytokine-positive cells decreased by day??7. These findings indicate that, in addition to macrophages, neutrophils, and fibroblasts, the JE cells are a potent source of TNF-??, IL-1??, and IL-1?? reacting to LPS application, and suggest that JE cells may play an important role in the first line of defense against LPS challenge, and the proinflammatory cytokines transiently produced by various host cells may be invo

Accumulating evidence indicates that an important event in the tissue response in periodontal disease is the recruitment of polymorphonuclear leukocytes (PMN). This study investigated immunohistochemical expression of CXC-chemokines, including macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant-2 (CINC-2) in rat periodontal tissue at 1 and 3 hours and 1, 2, 3 and 7 days after topical application of lipopolysaccharide (LPS; 5 mg/ml in saline) from E. Coli into the rat molar gingival sulcus. In normal periodontal tissues before LPS application, a small number of MIP-2 and CINC-2 positive cells were seen in junctional epithelium (JE) especially in its coronal half. After topical application of LPS, a prominent increase of MIP-2 and CINC-2 positive JE cells was observed. Almost all JE cells strongly expressed them at day 1 and day 2, and then the number of chemokine-positive cells returned to normal at day 7. Corresponding to these chemokine expressions, LPS application induced a significant increase in number of PMNs in sub-JE area at 1 hour (P <0.01) and 3 hours (P <0.05) and a significant increase in JE area at 1 day(P< 0.05) and 2 days (P <0.01), indicating a dynamic flow of PMNs from the sub-JE area into JE. These findings indicated that JE cells produced MIP-2 and CINC-2 in response to LPS stimulation and suggested that MIP-2 and CINC-2 may be responsible for PMN migration toward the periodontal pathogen and may play an important role in the initiation of inflammation and subsequent periodontal tissue destruction.