Impairment of gingival fibroblast adherence by IL-6/sIL-6R

Interleukin-6 (IL-6) binds to human gingival fibroblasts (HGF) in the prese nce of a soluble form of IL-6 receptor (sIL-6R). We investigated the effect s of IL-6 on the functions of HGF in the presence of sIL-6R. HGF changed th eir morphology from spindle-shaped to round, and detached from the culture dish by stimulation with IL-6/sIL-6R. In this condition, a signal transduce r gp130 and a transcription factor Stat3 were phosphorylated, resulting in activation of transcription factors Stat3 and C/EBP beta. Cytoskeletal beta -actin and adhesion molecule integrin-alpha5, a subunit of alpha (5)beta ( 1) integrin (VLA-5), were found to possess potential binding domains for th ese transcription factors in their promoters. Accumulation of beta -actin a nd integrin-alpha5 mRNA decreased, contrary to the expectation of the induc tion of gene transcription. Furthermore, the decrease in their mRNAs was as sociated with reduced expression of both actin and VLA-5 proteins. These re sults suggest that the expression of VLA-5 and actin was down-regulated in HGF through an IL-6 signaling pathway, resulting in impairment of HGF adher ence.