Mechanistic features associated with induction of metalloproteinases in human gingival fibroblasts by interleukin-1.
Human gingival fibroblasts were treated with recombinant interleukin-1 (IL-1) to determine the effect of this stimulus on the relative expression of collagenase (MMP-1), stromelysin (MMP-3) and plasminogen activator (PA) mRNA. The steady-state mRNA levels for these genes were determined on Northern blots. IL-1 induced steady-state levels of these mRNAs to different extents. Nuclear run-on transcription studies showed that IL-1 induction of neutral metalloproteinase may be transcriptionally regulated. Actinomycin D and protein kinase inhibitors decreased the mRNA production for all three metalloproteinases, whereas cycloheximide decreased the production of collagenase and stromelysin mRNA. Protein kinase inhibitors (H7/H8) decreased production of the three mRNAs to different extents. This study demonstrates a potentially important role for IL-1 in the regulation of metalloproteinase expression in human gingival fibroblasts. The ability of IL-1 to induce the expression of stromelysin, collagenase and PA may define a pivotal role for this cytokine in the pathogenesis of periodontitis.
Department of Biochemistry and Molecular Biology, Philadelphia College of Osteopathic Medicine, PA 19131-1696.
D S
DS
Tewari
Y
Y
Qian
M
M
Tewari
J
J
Pieringer
R D
RD
Thornton
R
R
Taub
E O
EO
Mochan
D015152:Blotting, Northern; D002478:Cells, Cultured; D017364:Collagenases / Q000096:biosynthesis / Q000235:genetics; D003513:Cycloheximide / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D005347:Fibroblasts / Q000201:enzymology*; D005881:Gingiva / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D020781:Matrix Metalloproteinase 1; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics; D010960:Plasminogen Activators / Q000096:biosynthesis / Q000235:genetics; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic
D007375:Interleukin-1; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D003513:Cycloheximide; D010960:Plasminogen Activators; D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1