Role of soluble interleukin-6 receptor in inflamed gingiva for binding of interleukin-6 to gingival fibroblasts

Interleukin-6 (IL-6), frequently detected in periodontitis, is known to med iate important signals in the inflammatory cytokine network. Gingival fibro blasts (GF) secrete cytokines upon stimulation with inflammatory mediators. However, it is not clear if GF respond to IL-6. We examined the lL-6 recep tor gene expression in GF. Furthermore, we tested whether GF are target cel ls for IL-6 by examination of binding of IL-6. GF were found to contain tra ce amounts of mRNA for IL-6 receptor (IL-GR), but had high levels of mRNA f or 130-kDa glycoprotein (gp130), which is a signal transducer for IL-6/IL-6 R complex. Based on this observation, we hypothesized that IL-6 could bind GF if exogenous soluble forms of IL-6R (sIL-6R) existed in the gingiva or c ulture condition. Thus, we investigated the existence of sIL-6R in gingiva using enzyme-linked immunosorbent assay and whether sIL-6R influenced the b inding of IL-6 to GF in vitro. In inflamed gingiva, sIL-6R was detected and its concentration ranged from 150 to 700 pg/mu g protein. The sIL-6R enhan ced the binding of IL-6 to GF in a dose-dependent manner. This enhancement was inhibited by an antibody against gp130, suggesting that the IL-6/sIL-6R complex bound to the fibroblasts via gp130. These data demonstrated that g ingival fibroblasts can be target cells for IL-6 in the presence of appropr iate amounts of sIL-6R. This situation may exist during inflammation in per iodontal tissue.