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The Role of Soluble Interleukin (IL)‐6 Receptor in Mediating the effects of IL‐6 on Matrix Metalloproteinase‐1 and Tissue Inhibitor of Metalloproteinase‐1 Expression by Gingival Fibroblasts
Author(s) -
Irwin Chris R.,
Myrillas Theofilos T.,
Traynor Patrick,
Leadbetter Nicola,
Cawston Timothy E.
Publication year - 2002
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1902/jop.2002.73.7.741
Subject(s) - matrix metalloproteinase , fibroblast , receptor , tissue inhibitor of metalloproteinase , chemistry , microbiology and biotechnology , downregulation and upregulation , interleukin , cytokine , matrix (chemical analysis) , receptor expression , endocrinology , medicine , andrology , immunology , biology , biochemistry , in vitro , chromatography , gene
Background: Interleukin‐6 (IL‐6) is a multifunctional cytokine thought to play a role in the tissue destruction that characterizes periodontal disease. IL‐6 exerts its cellular effects through a cell‐surface receptor which also exists in a soluble from (sIL‐6r). This study investigated the effects of IL‐6 on matrix metalloproteinase (MMP)‐1 activity in gingival fibroblast cultures, specifically determining the role of the sIL‐6r in mediating these actions. Methods: Fibroblasts were grown to confluence, washed in Hank's balanced saline solution (HBSS), and then cultured for 72 hours in serum‐free medium supplemented with 0.2% bovine serum albumin, 1 µg/ml Escherichia coli LPS and containing various combinations of IL‐6 and its soluble receptor over the concentration range 0 to 1,000 ng/ml. MMP‐1 and tissue inhibitor of MMP (TIMP)‐1 protein levels in the conditioned medium were assessed by enzyme‐linked immunosorbent assay (ELISA) and collagenolytic activity determined using a 3 H‐acetylated type 1 collagen degradation assay. Results: Results indicated that the addition of IL‐6 alone to cultures, over the concentration range 0 to 1,000 ng/ml, had no significant effect on MMP‐1 protein expression. However, addition of IL‐6 in combination with its soluble receptor resulted in a statistically significant, dose‐dependent upregulation in MMP‐1 expression. The IL‐6/slL‐6r combination also induced a significant increase in collagenolytic activity in cultures. IL‐6 and slL‐6r, either alone or in combination, had no marked effect on TlMP expression or cell growth. Conclusions: These data strongly suggest that future clinical studies investigating the role of IL‐6 in periodontal disease must also determine the levels of slL‐6r within the periodontal tissues. J Periodontol 2002;73:741‐747.