Effects of exogenous IL-1β, TNFα, IL-6, IL-8 and LIF on cytokine production by human articular chondrocytes

Henrotin, Yves; Groote, Donat De; Labasse, A; Gaspar, Simone E.; Shao-xiong, Zheng; Geenen, Vincent; Reginster, Jean-Yves

doi:10.1016/s1063-4584(96)80012-4

Cited by 70 publications

(48 citation statements)

References 31 publications

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“…Treatment with TNF␣, either alone or in combination with injury, dramatically increased chondrocyte synthesis of endogenous IL-6 ( Figure 5); this finding is consistent with the results of previous studies showing that IL-1 and TNF␣ greatly increase the production of IL-6 (46). To test whether endogenous IL-6 plays a role in proteoglycan degradation caused by injury plus TNF␣ treatment, we treated explants with an anti-IL-6 Fab fragment and found that GAG loss was significantly decreased ( Figure 6).…”

supporting

confidence: 91%

Mechanical injury potentiates proteoglycan catabolism induced by interleukin‐6 with soluble interleukin‐6 receptor and tumor necrosis factor α in immature bovine and adult human articular cartilage

Sui¹,

Lee²,

DiMicco³

et al. 2009

Arthritis & Rheumatism

110

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Objective. Traumatic joint injury can damage cartilage and release inflammatory cytokines from adjacent joint tissue. The present study was undertaken to study the combined effects of compression injury, tumor necrosis factor ␣ (TNF␣), and interleukin-6 (IL-6) and its soluble receptor (sIL-6R) on immature bovine and adult human knee and ankle cartilage, using an in vitro model, and to test the hypothesis that endogenous IL-6 plays a role in proteoglycan loss caused by a combination of injury and TNF␣.Methods. Injured or uninjured cartilage disks were incubated with or without TNF␣ and/or IL-6/sIL-6R. Additional samples were preincubated with an IL-6-blocking antibody Fab fragment and subjected to injury and TNF␣ treatment. Treatment effects were assessed by histologic analysis, measurement of glycosaminoglycan (GAG) loss, Western blot to determine proteoglycan degradation, zymography, radiolabeling to determine chondrocyte biosynthesis, and Western blot and enzyme-linked immunosorbent assay to determine chondrocyte production of IL-6.Results. In bovine cartilage samples, injury combined with TNF␣ and IL-6/sIL-6R exposure caused the most severe GAG loss. Findings in human knee and ankle cartilage were strikingly similar to those in bovine samples, although in human ankle tissue, the GAG loss was less severe than that observed in human knee tissue. Without exogenous IL-6/sIL-6R, injury plus TNF␣ exposure up-regulated chondrocyte production of IL-6, but incubation with the IL-6-blocking Fab significantly reduced proteoglycan degradation.Conclusion. Our findings indicate that mechanical injury potentiates the catabolic effects of TNF␣ and IL-6/sIL-6R in causing proteoglycan degradation in human and bovine cartilage. The temporal and spatial evolution of degradation suggests the importance of transport of biomolecules, which may be altered by overload injury. The catabolic effects of injury plus TNF␣ appeared partly due to endogenous IL-6, since GAG loss was partially abrogated by an IL-6-blocking Fab.Osteoarthritis (OA) is a highly prevalent joint disease characterized by progressive degradation and loss of articular cartilage. Joint injury in young adults dramatically increases the risk for developing OA (1,2). Acute knee injury, such as anterior cruciate ligament tear, can subject cartilage to high mechanical stress and is accompanied by an increase in synovial fluid levels of matrix metalloproteinase 3 (MMP-3) (3) and multiple

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supporting

confidence: 91%

Mechanical injury potentiates proteoglycan catabolism induced by interleukin‐6 with soluble interleukin‐6 receptor and tumor necrosis factor α in immature bovine and adult human articular cartilage

Sui¹,

Lee²,

DiMicco³

et al. 2009

Arthritis & Rheumatism

110

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“…On the other hand, IL-6 is necessary for the IL-1-induced inhibition of proteoglycan synthesis in human articular cartilage [41]. Finally, we have also demonstrated that IL-6 is able to inhibit partially the spontaneous production of IL-8 by chondrocytes [42]. Consequently, we must be cautious in considering the real physiopathological implication of the inhibition of IL-6 production by A/S unsaponifiable mixtures.…”

Section: Discussionmentioning

confidence: 84%

Effects of three avocado/soybean unsaponifiable mixtures on metalloproteinases, cytokines and prostaglandin E2 production by human articular chondrocytes

Henrotin

Labasse

Jaspar³

et al. 1998

Clin Rheumatol

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The in-vitro effects of avocado and soybean unsaponifiable residues on neutral metalloproteinase activity, cytokines and prostaglandin E2 (PGE2) production by human articular chondrocytes were investigated. Avocado and soybean unsaponifiable residues were mixed in three ratios: 1:2 (A1S2), 2:1 (A2S1) or 1:1 (A2S2). Freshly isolated human chondrocytes were cultured for 72 h in the absence or presence of interleukin-1beta, (IL-1beta) (17 ng/ml), with or without unsaponifiable residue mixtures at a concentration of 10 microg/ml. A/S unsaponifiable residues were also tested separately at concentrations of 3.3, 6.6 and 10 microg/ml. All A/S unsaponifiable mixtures reduced the spontaneous production of stromelysin, interleukin-6 (IL-6), interleukin-8 (IL-8) and prostaglandin E2 (PGE2) by chrondrocytes. At concentrations of 3.3 and 6.6 microg/ml, A/S residues, tested separately, were potent inhibitors of the production of IL-8 and PGE2. Nevertheless, only avocado residue inhibited IL-6 production at these concentrations. A/S unsaponifiable mixtures had a more pronounced inhibitory effect on cytokine production than avocado or soybean residues added alone. As anticipated, IL-1beta induced a marked release of collagenase, stromelysin, IL-6, IL-8 and PGE2. A/S unsaponifiable mixtures partially reversed the IL-1 effects on chrondrocytes. These findings suggest a potential role for A/S unsaponifiable extracts in mitigating the deleterious effects of IL-1beta: on cartilage.

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“…5,9,10 In line with our IL-1 expression data, no significant induction of IL-6 was observed in osteoarthritic chondrocytes in situ, though this gene is strongly induced by IL-1␤ in articular chondrocytes. 16,18 The observed minor changes in cytokine expression levels might be due to a selective zonal induction of IL-1␤, which, as discussed below, could be important in mediating matrix degradation as well as normal matrix homeostasis. The presence of low IL-1␤ bioactivity was, however, documented by the significant coexpression patterns of IL-6 with IL-1␤ in osteoarthritic cartilage.…”

Section: Discussionmentioning

confidence: 99%

Activation of Interleukin-1 Signaling Cascades in Normal and Osteoarthritic Articular Cartilage

Fan

Söder

Oehler³

et al. 2007

The American Journal of Pathology

119

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Interleukin (IL)-1 is one of the most important catabolic cytokines in rheumatoid arthritis. In this study, we were interested in whether we could identify IL-1 expression and activity within normal and osteoarthritic cartilage. mRNA expression of IL-1␤ and of one of its major target genes, IL-6, was observed at very low levels in normal cartilage, whereas only a minor up-regulation of these cytokines was noted in osteoarthritic cartilage, suggesting that IL-1 signaling is not a major event in osteoarthritis. However, immunolocalization of central mediators involved in IL-1 signaling pathways [38-kd protein kinases, phospho (P)-38-kd protein kinases, extracellular signal-regulated kinase 1/2, P-extracellular signal-regulated kinase 1/2, c-Jun NH 2 -terminal kinase 1/2, P-c-Jun NH 2 -terminal kinase 1/2, and nuclear factor B] showed that the four IL-1 signaling cascades are functional in normal and osteoarthritic articular chondrocytes. In vivo, we found that IL-1 expression and signaling mechanisms were detectible in the upper zones of normal cartilage, whereas these observations were more pronounced in the upper portions of osteoarthritic cartilage. Given these expression and distribution patterns, our data support two roles for IL-1 in the pathophysiology of articular cartilage. First, chondrocytes in the upper zone of osteoarthritic articular cartilage seem to activate catabolic signaling pathways that may be in response to diffusion of external IL-1 from the synovial fluid. Second, IL-1 seems to be involved in normal cartilage tissue homeostasis as shown by identification of baseline expression patterns and signaling cascade activation.

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Effects of exogenous IL-1β, TNFα, IL-6, IL-8 and LIF on cytokine production by human articular chondrocytes

Cited by 70 publications

References 31 publications

Mechanical injury potentiates proteoglycan catabolism induced by interleukin‐6 with soluble interleukin‐6 receptor and tumor necrosis factor α in immature bovine and adult human articular cartilage

Mechanical injury potentiates proteoglycan catabolism induced by interleukin‐6 with soluble interleukin‐6 receptor and tumor necrosis factor α in immature bovine and adult human articular cartilage

Effects of three avocado/soybean unsaponifiable mixtures on metalloproteinases, cytokines and prostaglandin E2 production by human articular chondrocytes

Activation of Interleukin-1 Signaling Cascades in Normal and Osteoarthritic Articular Cartilage

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