Tumor necrosis factor-a (TNF-
a) is one of proinflammatory cytokines produced as early inflammatory responses, and is suggested to partici-pate in the establishment of inflammatory lesions. To understand the regulatory role of TNF-
a on periodontal connective tissue, we evaluated the effect of TNF-
a on DNA synthesis, collagenous and non-collagenous protein synthesis, prostaglan-din E
2 (PGE
2) productivity, and platelet-derived growth factor (PDGF) -A chain mRNA expression in human gingival fibroblasts (HGF).
Results indicated that 1) TNF-
a promoted DNA synthesis, both collagenous and non-col-lagenous protein synthesis in HGF, 2) TNF-
a markedly enhanced PGE
2 production in HGF, 3) inhibition of PGE
2 synthesis by the addition of in-domethacin, further augmented the ability of DNA synthesis and collagenous and non-collagenous pro-tein synthesis in HGF, and 4) TNF-
a enhanced the expression of PDGF-A chain mRNA in HGF.
These results suggest that TNF-
a enhances the DNA synthesis and extracellular matrix protein synthesis in HGF, but endogenous PGE
2 which is induced by TNF-
a, partially blocks these effects. Furthermore, the enhancement of DNA synthesis in response to TNF-
a could be possibly mediated by autocrine PDGF.
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