[en] Cytokines are potent regulators of the chondrocyte functions. Some of them are produced by chondrocytes and interact to regulate cartilage metabolism. In this study, we investigated the production of interleukin-1 beta (IL-1 beta), IL-6, IL-8 and leukemia inhibitory factor (LIF) by human chondrocytes and examined the modulation of their secretion by exogenous cytokines. Human articular chondrocytes were isolated from their extracellular matrix by a triple successive enzymatic digestion of the cartilage. Subsequently, chondrocytes were stimulated by increased amounts of human recombinant cytokines [IL-1 beta, tumour necrosis factor alpha (TNF alpha), IL-8, LIF, IL-6]. IL-1 beta, IL-6, IL-8 and LIF were assayed into culture media and inside cell extracts by specific enzyme amplified sensitivity immunoassays (EASIAs). Under these experimental conditions, we have identified various interactions between cytokines. IL-beta and TNF alpha highly stimulated IL-6, LIF and IL-8 productions. IL-6 decreased IL-8 synthesis and increased LIF production. IL-8 slightly enhanced IL-6 production. Finally, LIF stimulated IL-1 beta, IL-6 and IL-8 productions. Using neutralizing antibodies against IL-1, we demonstrated that the effects of LIF were secondary to the stimulation by LIF of IL-1 beta production by the chondrocytes. In conclusion, chondrocytes secrete a variety of immunocompetent cytokines including IL-1 beta, IL-6, IL-8 and LIF that can interact to regulate chondrocytes metabolism. These results also define new biological activities of LIF and IL-6, and raise questions concerning their role in the pathogenesis of joint diseases.
Disciplines :
Rheumatology
Author, co-author :
Henrotin, Yves ; Université de Liège - ULiège > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.)
De Groote, D. D.
Labasse, A. H.
Gaspar, S. E.
Zheng, S. X.
Geenen, Vincent ; Université de Liège - ULiège > Centre d'immunologie
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé
Language :
English
Title :
Effects of exogenous IL-1 beta, TNF alpha, IL-6, IL-8 and LIF on cytokine production by human articular chondrocytes.
Houssiau, FA, Devoegelaer, JP, Van Damme, J, Nagant de Deuxschaine, C, Van Snik, J, Interleukin-6 in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides (1988) Arthritis Rheum, 31 (6), pp. 784-788
Waring, P, Wycherly, K, Cary, D, Nicola, N, Metcalf, D, Leukaemia inhibitory factor (LIF) levels are elevated in septic shock and various inflammatory body fluids (1992) J Clin Invest, 90, pp. 2031-2037
Kahle, P, Saal, JG, Schaudt, K, Zacher, J, Fritz, P, Pawelec, G, Determination of cytokines in synovial fluids: correlation with diagnosis and histomorphological characteristics of synovial tissue (1992) Ann Rheum Dis, 51, pp. 731-734
Martel-Pelletier, J, Zafarullah, M, Kodama, S, Pelletier, JP, In vitro effects of interleukin 1 on the synthesis of metalloproteases, TIMP, plasminogen activators and inhibitors in human articular cartilage (1991) J Rheumatol, 18 (Suppl 27), pp. 80-84
Lefebvre, V, Peeters-Joris, C, Vaes, G, Modulation by interleukin 1 and tumor necrosis factor α of production of collagenase, tissue inhibitor of metalloproteinases and collagen type in differentiated and dedifferentiated articular chondrocytes (1990) Biochim Biophys Acta, 1052, pp. 366-378
Tiku, M, Liesch, JB, Robertson, FM, Production of hydrogen peroxide by rabbit articular chondrocytes. Enhancement by cytokines (1990) J Immunol, 145 (2), pp. 690-696
Ahmadzadeh, N, Shingu, M, Nobunaga, M, The effect of recombinant tumor necrosis factor-α on superoxide and metalloproteinases production by synovial cells and chondrocytes (1990) Clin Exp Rheumatol, 8, pp. 387-391
Yaron, I, Meyer, FA, Dayer, JM, Bleiberg, I, Yaron, M, Some recombinant human cytokines stimulate glycosaminoglycan synthesis in human synovial fibroblasts cultures and inhibit it in human articular cartilage cultures (1989) Arthritis Rheum, 32 (2), pp. 173-180
Goldring, MB, Birkhead, J, Sandell, LJ, Kimura, T, Krane, SM, Interleukin 1 suppresses expression of cartilage specific type II and IX collagens and increases type I and III collagens in human chondrocytes (1988) J Clin Invest, 82, pp. 2026-2037
Konig, A, Buhlbauer, RC, Fleisch, H, Tumor necrosis factor α and interleukin 1 stimulate bone resorption in vivo as measured by urinary 3-H tetracycline excretion from prelabeled mice (1988) J Bone Miner Res, 3 (6), pp. 621-627
Henderson, B, Pettipher, ER, Arthrogenic actions of recombinant IL-1 and tumor necrosis factor α in the rabbit: evidence for synergistic interactions between cytokines in vivo (1989) Clin Exp Immunol, 75, pp. 306-310
Bandara, G, Georgescu, HI, Lin, CW, Evans, CH, Synovial activation of chondrocytes: evidence for complex cytokine interactions (1991) Agents Actions, 34, pp. 285-288
Splawski, JB, McAnally, LM, Lipsky, PE, IL-2 dependence of the promotion of human B cell differentiation by IL-6 (BSF-2) (1990) J Immunol, 144 (2), pp. 562-569
Gauldie, J, Northemann, W, Fey, G, IL-6 functions as an exocrine hormone in inflammation. Hepatocytes undergoing acute phase responses require exogenous IL-6 (1990) J Immunol, 144 (10), pp. 3804-3808
Malfait, AM, Verbruggen, G, Veys, E, Lambert, J, De Ridder, L, Cornelissen, M, Comparative and combined effects of interleukin 6, interleukin 1β, and tumor necrosis factor α on proteoglycan metabolism of human articular chondrocytes cultured in agarose (1994) J. Rheumatol, 21, pp. 314-320
Seckinger, P, Yaron, I, Meyer, FA, Yaron, M, Dayer, JM, Modulation of the effects of interleukin-1 on glycosaminoglycan synthesis by urine derived interleukin-1 inhibitor but not by interleukin-6 (1990) Arthritis Rheum, 33 (12), pp. 1807-1814
Nietfield, JJ, Wilbrink, B, Helle, M, Van Roy, JLAM, Den Otter, W, Swaak, AJG, Huber-Bruning, O, Interleukin-1-induced interleukin-6 is required for the inhibition of proteoglycan synthesis by interleukin-1 in human articular cartilage (1990) Arthritis Rheum, 33 (11), pp. 818-826
Lotz, M, Guerne, PA, Interleukin-6 induces the synthesis of tissue inhibitor of metalloproteinases-1/erythroid potentiating activity (TIMP-1/EPA) (1991) J Biol Chem, 266 (4), pp. 2017-2020
Villigher, PM, Kusari, AB, Ten Dijke, P, Lotz, M, IL-1β and IL-6 selectively induce transforming growth factor-β isoforms in human articular chondrocytes (1993) J Immunol, 151 (6), pp. 3337-3344
Guerne, PA, Zuraw, BL, Vaughan, JH, Carson, PA, Lotz, M, Synovium as a source of interleukin-6 in vitro. Contribution to local and systemic manifestations of arthritis (1988) J Clin Invest, 83 (2), pp. 585-592
Peveri, P, Waltz, A, Dewald, B, Baggiolini, M, A novel neutrophil-activating factor produced by human mononuclear phagocytes (1988) J Exp Med, 167 (5), pp. 1547-1559
Elford, PR, Cooper, PH, Induction of neutrophil-mediated cartilage degradation by IL-8 (1991) Arthritis Rheum, 34 (3), pp. 325-331
Abe, T, Murakami, M, Sato, T, Kajiki, M, Ohno, M, Kodaira, R, Macrophage differentiation inducing factor from human monocytic cells is equivalent to murine leukemia inhibitory factor (1989) J Biol Chem, 264 (15), pp. 8941-8945
Williams, RL, Hilton, DJ, Pease, S, Willson, TA, Stewart, CL, Gearing, DP, Wagner, EF, Gough, NM, Myeloid leukaemia inhibitory factor maintains the developmental potential of embryon stem cells (1988) Nature (London), 336, pp. 684-687
Bauman, HH, Wong, GG, Hepatocyte-stimulating factor III shares structural and functional identity with leukemia inhibitory factor (1988) J Immunol, 143 (4), pp. 1163-1167
Murphy, M, Reid, K, Hilton, DJ, Bartleff, PF, Generation of sensory neurons is stimulated by leukemia inhibitory factor (1991), pp. 3498-3501
Metcalf, D, Nicola, NA, Gearing, JP, Effects of injected leukemia inhibitory factor on haematopoietic and other tissues in mice (1990) Blood, 76 (1), pp. 50-56
Freidin, M, Kessleer, JA, Cytokine regulation of substance P expression in sympathetic neurons (1991), pp. 3200-3203
Allan, EH, Hilton, DJ, Brown, M, Evely, RS, Yumita, S, Metcalf, D, Gough, NM, Martin, TJ, Osteoblasts display receptors for and responses to leukemia inhibitory factor (1990) J Cell Physiol, 145, pp. 110-119
Ishimi, Y, Abe, E, Jin, CH, Miyaura, C, Hong, MH, Kurosawa, H, Yamaguchi, Y, Suda, T, Leukaemia inhibitory factor (LIF/D-Factor): regulation of its production and possible roles in bone metabolism (1992) J Cell Physiol, 152, pp. 71-78
Guerne, PA, Carson, DA, Lotz, M, IL-6 production by human articular chondrocytes. Modulation of its synthesis by cytokines, growth factors, and hormones in vitro (1990) J Immunol, 144 (2), pp. 499-505
Villigher, PM, Geng, Y, Lotz, M, Induction of cytokine expression by leukemia inhibitory factor (1993) J Clin Invest, 91, pp. 1575-1581
De Groote, D, Zangerle, PF, Gevaert, Y, Fassote, MF, Beguin, Y, Noizat-Pirenne, MF, Pirenne, J, Franchimont, P, Direct stimulation of cytokines (IL-1β, TNFα, IL-6, IL-2, IFN, and GM-CSF) in whole blood. Comparison with isolated PBMC stimulation (1992) Cytokine, 4 (3), pp. 239-248
Labarca, A, Paigen, K, A simple, rapid and sensitive DNA procedure (1980) Anal Biochem, 102 (2), pp. 344-354
Zerbe, GO, Randomization analysis of the completely randomized design extended to growth and response curves (1979) J Am Stat Assoc, 74, pp. 215-224
Kandel, RA, Petelycky, M, Dinarello, CA, Minden, M, Printzker, KPH, Cruz, TF, Comparison of the effect of interleukin 6 and interleukin 1 on collagenase and proteoglycan production by chondrocytes (1990) J Rheumatol, 17, pp. 953-957
Lotz, M, Jirik, F, Kaboudiris, R, Tsoukas, C, Hirano, T, Kishimoto, T, Carson, DA, BSF-2/IL-6 is a costimulant for human thymocytes and T lymphocytes (1988) J Exp Med, 167 (5), pp. 1253-1258
Van de Loo, FAJ, Joosten, LAB, Van Lent, PLEM, Arntz, JO, Van den Berg, WB, Role of interleukin-1, tumor necrosis factor α, and interleukin-6 in cartilage proteoglycan metabolism and destruction (1995) Arthritis Rheum, 38 (2), pp. 164-172
Lotz, M, Moats, T, Villigher, PM, Leukaemia inhibitory factor is expressed in cartilage and synovium and can contribute to the pathogenesis of arthritis (1992) J Clin Invest, 90 (3), pp. 888-896
Henrotin, Y, Labasse, A, Reginster, JY, Franchimont, P, Effect du Leukaemia inhibitory factor (LIF) sur le metabolisme des chondrocytes articulaires humains in vitro (abstract) (1993) Rev Rhum, 60 (10), p. 682
