Interleukin‐1β induces synthesis and secretion of interleukin‐6 in human chondrocytes

Abstract

Increased concentrations of interleukin‐6 (IL‐6) have been found in the synovial fluid of patients with osteoarthritis, rheumatoid arthritis and crystal‐related joint deseases. It is therefore of great interest to identify the cells responsible for the production of IL‐6, and to investigate whether IL‐6 plays a role in the pathogenesisof degenerative or inflammatory joint diseases. Here we show that human interleukin‐1β (IL‐1β) induces IL‐6 synthesis and secretion in differentiated human chondrocytes. In organ cultures resembling closely the in vivo system 106 chondrocytes incubated with 100 units of interleukin‐1β per ml of medium led to the release of 6 × 103 units of IL‐6 within 24 h. Chondrocytes cultured in agarose or as monolayers similary incubated with IL‐1β produced even higher amounts of IL‐6: 70 × 103 units per 106 cells within 24 h. The induction of IL‐6 synthesis by IL‐1β was also shown at the mRNA level. IL‐6 secreted by stimulated chondrocytes showed heterogeneity upon Western blot analysis.

JAK/STAT but Not ERK1/ERK2 Pathway Mediates Interleukin (IL)-6/Soluble IL-6R Down-regulation of Type II Collagen, Aggrecan Core, and Link Protein Transcription in Articular Chondrocytes

“…and tumor necrosis factor-␣ can also stimulate the production of IL-6 by articular cartilage chondrocytes (56,57). As previously reported by others (34, 55), we found that the effect of IL-6 requires the presence of its soluble receptor (sIL-6R) in the culture medium.…”

Transforming Growth Factor β1 Regulates Tissue Inhibitor of Metalloproteinases—1 Expression in Differentiated Human Articular Chondrocytes

“…Furthermore, we (21) and others (22,23) found IL-1 to be a strong inducer of IL-6 synthesis and secretion in human chondrocytes. This observation raised the question of whether IL-6 may act on these cells in an autocrine manner.…”

“…Whereas Guerne et al (22) found that chondrocytes in monolayer culture without stimulation released 200 B9 units of IL-6 per milliliter of medium within 72 hours, several experiments with our agarose cultures yielded 3,200-50,000 B9 units of IL-6 per milliliter of medium in 72 hours. Also, in monolayer cultures, we recently found 3,100 B9 units of IL-6 per milliliter within 24 hours (21). From dose-response experiments in other systems, we know that 200 B9 units per milliliter of medium, as found by Guerne et a1 (22), is not sufficient for the stimulation of IL-6-responsive genes.…”

Pathogenesis of Degenerative Joint Disease in the Human Temporomandibular Joint

“…Cytokines that have been implicated in degenerative joint disease are interleukin-1 (Chang et al, 1986(Chang et al, , 1992Goldring et al, 1988;Verschure and Van, 1990;Davies et al, 1992), tumor necrosis factor (Campbell et al, 1990a,b;Pickvance et al, 1993), interleukin-6 (Bender et al, 1990), andinterleukin-8 (DeMarco et al, 1991;Elford and Cooper, 1991). Collectively, these cytokines increase fibrocartilage degradation by stimulating the synthesis of matrix-degrading enzymes by local cell populations.…”