Tumor necrosis factor-alpha (TNF-alpha)-induced and interleukin-1 beta (IL-1 beta)-induced shedding of TNF receptors from gingival fibroblasts

Tumor necrosis factor-alpha (TNF-alpha) exerts its functions by binding two different receptors (TNFR55 and TNFR75), Both TNFR55 and TNFR75 exist in c ell-associated and soluble forms. Soluble TNF receptors (sTNFR), sTNFR55 an d sTNFR75, are proteolytically shed upon inflammatory stimuli and then modu late various TNF-alpha bioactivities. As human gingival fibroblasts (HGF) c an be potential targets for TNF-alpha in inflamed gingiva, we hypothesized that HGF partially modulate the cellular responses to TNF-alpha by regulati ng their own TNFR. In this study, the kinetics of expression of cell-associ ated and soluble forms of both receptors from cultured HGF in response to p roinflammatory cytokines TNF-alpha and interleukin-1 beta (IL-1 beta) were investigated in vitro. Both TNF-alpha and IL-1 beta upregulated the gene ex pression of TNFR75 and did not affect that of TNFR55. TNF-alpha and IL-1 be ta decreased binding of [I-125]TNF-alpha to HGF. Moreover, TNF-alpha and IL -1 beta upregulated the release of sTNFR75 from HGF but not that of sTNFR55 , These results suggest that HGF under inflammatory conditions may contribu te to the inactivation of circulating TNF-a through the preferential induct ion and shedding of TNFR75.