INTERLEUKIN-1-BETA AND TUMOR-NECROSIS-FACTOR-ALPHA STIMULATE SYNERGISTICALLY THE EXPRESSION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN FIBROBLASTIC CELLS DERIVED FROM HUMAN PERIODONTAL-LIGAMENT

The present study demonstrates that interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) induce and synergistically st imulate monocyte chemoattractant protein-1 (MCP-1) expression in fibro blasts from human periodontal ligament. IL-1 beta and TNF-alpha induce d in a dose-dependent manner the expression of the MCP-1 gene in the f ibroblasts from the human periodontal ligament. However, such an induc ing effect was not observed with IL-6 interferon-gamma. The peak expre ssion of the MCP-1 gene by IL-1 beta or TNF-alpha was observed at 3 h after initiation of their treatment. Furthermore, IL-1 beta in combina tion with TNF-alpha synergistically stimulated the MCP-I gene expressi on in the cells. We also observed significant chemotactic activity for human monocytes in conditioned medium of fibroblasts from the human p eriodontal ligament treated with both cytokines. The stimulated chemot actic activity induced by these cytokines depended on both dose and tr eatment time. The chemotactic activity in conditioned medium of IL-1 b eta-treated fibroblasts from the human periodontal ligament was neutra lized by antiserum specific for MCP-1 protein. The MCP-1 gene product in conditioned medium of IL-1 beta-treated fibroblasts from the human periodontal ligament was shown to have a molecular mass of 11000 Da by immunoprecipitation with the specific antiserum, and IL-1 beta also s timulated synergistically MCP-1 protein expression in combination with TNF-alpha. These results suggest that IL-1 beta and TNF-alpha may con tribute to the infiltration of monocytes into inflammatory sites of pe riodontal ligament tissues via the MCP-1 gene product produced by fibr oblasts from the human periodontal ligament.