Impairment of gingival fibroblast adherence by IL-6/sIL-6R.
Interleukin-6 (IL-6) binds to human gingival fibroblasts (HGF) in the presence of a soluble form of IL-6 receptor (sIL-6R). We investigated the effects of IL-6 on the functions of HGF in the presence of sIL-6R. HGF changed their morphology from spindle-shaped to round, and detached from the culture dish by stimulation with IL-6/sIL-6R. In this condition, a signal transducer gp130 and a transcription factor Stat3 were phosphorylated, resulting in activation of transcription factors Stat3 and C/EBPbeta. Cytoskeletal beta-actin and adhesion molecule integrin-alpha5, a subunit of alpha5beta1 integrin (VLA-5), were found to possess potential binding domains for these transcription factors in their promoters. Accumulation of beta-actin and integrin-alpha5 mRNA decreased, contrary to the expectation of the induction of gene transcription. Furthermore, the decrease in their mRNAs was associated with reduced expression of both actin and VLA-5 proteins. These results 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 adherence.
Naruishi
K
K
Department of Patho-physiology, Periodontal Science, Okayama University Graduate School of Medicine and Dentistry, Japan.
Takashiba
S
S
Nishimura
F
F
Chou
H H
HH
Arai
H
H
Yamada
H
H
Murayama
Y
Y
D000199:Actins / Q000096:biosynthesis; D000595:Amino Acid Sequence; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D058966:Contactins; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005891:Gingivitis / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding / Q000187:drug effects; D017469:Receptors, Fibronectin / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000378:metabolism; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism
D000199:Actins; D058966:Contactins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D019006:Neural Cell Adhesion Molecules; D017469:Receptors, Fibronectin; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; C104543:interleukin 6-interleukin 6 receptor fusion protein, recombinant