Production of Rantes/CCL5 in human gingival fibroblasts challenged with tumor necrosis factor alpha

Chemokines are small-secreted proteins that stimulate the directional migra tion of leukocytes and thereby mediate the inflammatory process. The presen t study investigates the capacity of human gingival fibroblasts to produce the beta chemokine Rantes/CCL5. In situ hybridization, immunohistochemistry and ELISA were used to measure the induction of Rantes/CCL5 at the mRNA an d protein levels, both in unstimulated gingival fibroblasts as well as in f ibroblasts treated with the proinflammatory cytokines tumor necrosis factor (TNF)alpha or interleukin (IL)-1 beta. TNF alpha in different concentratio ns (0.1-10 ng/ml) induced Rantes/CCL5 mRNA expression and protein productio n in 24-h cultures of human gingival fibroblasts. The expression of Rantes/ CCL5-mRNA and protein production, induced by TNF alpha, was evident at 6 h and thereafter increased continuously during the study period (24 h). IL-1 beta (3-300 pg/ml) also enhanced the production of Rantes/CCL5 in gingival fibroblasts. The amount of Rantes/CCL5 induced by IL-1 beta (300 pg/ml), ho wever, was less than that induced by TNF alpha (10 ng/ml). The study sugges ts that human gingival fibroblasts, by producing the chemokine Rantes/CCL5, participate in the regulation of the host response during the inflammatory process in the periodontal tissue.