title: Blockade of recombinant human IL-6 by tocilizumab suppresses matrix metalloproteinase-9 production in the C28/I2 immortalized human chondrocyte cell line.
abstract: Two immortalized human juvenile chondrocyte cell lines, T/C28a2 and C28/I2, were employed to determine the extent to which recombinant human (rh) IL-6 or rh-TNF-α increased the production of matrix metalloproteinase-9 (MMP-9). The effect of rhIL-6 on neutrophil gelatinase-associated lipocalin (NGAL) was also assessed. Although C28/I2 chondrocytes incubated with rhIL-6 (50 ng/ml) increased MMP-9 production which could not be mimicked by the T/C28a2 chondrocyte line, the effect of rhTNF-α on MMP-9 was more robust than with rhIL-6. The combinations of rhIL-6 and soluble IL-6 receptor-α (sIL-6Rα) or rhIL-6 and tocilizumab (TCZ), a fully-humanized recombinant monoclonal antibody that neutralizes the interaction between IL-6 and IL-6R significantly reduced MMP-9 production by C28/I2 chondrocytes. However, TCZ had no effect on rhTNF-α-induced MMP-9 production. By contrast, rhIL-6 did not increase the production of NGAL by C28/I2 chondrocytes although the number of NGAL-positive cells was significantly reduced by sIL-6R compared to its control group, but not by the combination of rhIL-6 plus TCZ compared to rhIL-6. In summary, these results showed that rhIL-6 stimulated the production of MMP-9, but not NGAL, in the C28/I2 chondrocyte line. TCZ or sIL-6Rα suppressed rhIL-6-induced MMP-9 production.
authors.affiliation: Department of Medicine, Division of Rheumatic Diseases, Department of Reproductive Biology, Case Western Reserve University School of Medicine, USA.
authors.forename: Evan C
authors.initials: EC
authors.lastname: Meszaros
authors.affiliation: Department of Medicine, Department of Obstetrics and Gynecology, University Hospitals Case Medical Center, Cleveland, OH 44106 USA.
authors.forename: Wissam
authors.initials: W
authors.lastname: Dahoud
authors.affiliation: Department of Medicine, Department of Obstetrics and Gynecology, University Hospitals Case Medical Center, Cleveland, OH 44106 USA.
authors.forename: Sam
authors.initials: S
authors.lastname: Mesiano
authors.affiliation: Department of Medicine, Division of Rheumatic Diseases, Department of Reproductive Biology, Case Western Reserve University School of Medicine, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Malemud
keywords: IL-6; c28/i2 immortalized human chondrocyte; matrix; metalloproteinase-9; tocilizumab