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Rôle et mécanisme d'action de 2 cytokines pro-inflammatoires, interleukine-1B et interleukine-17, dans la dégénérescence du cartilage au cours des arthropathies

Abstract : Studies showed that cartilage damages, appearing during arthropathies, are due mainly to the presence of cytokines pro-inflammatory, such as interleukine-1 (IL-1) for which early effects in the cartilage are well established, while few data are available concerning the later answer of chondrocytes. Recently, works demonstrate a production in the joint of a new cytokine pro-inflammatory, interleukine-17 (IL-17). Because of its biologic properties, especially its capacity to stimulate the synthesis of pro-inflammatory cytokines, it could constitute an essential pathological factor in the destruction of articular cartilage. These 2 pro-inflammatory agents are both able to stimulate the production of NO for which the role on cartilage is today widely accepted. So, the objective of our study was to evaluate the contribution and the mechanisms of IL-1 and IL-17 in cartilage degradation. Then, we tried to better unc\erstand the relations between the NO production and the decrease of proteoglycans synthesis. Our in vitro (chondrocytes cultured in alginate beads or anatomical entities of rats) and in vivo results showed that IL-17 reproduces sorne of IL-1 effects on cartilage, especially a decrease of proteoglycans biosynthesis and a NO production, independently of any expression of IL-l. However, IL-17 dîffers of IL-1 because it leads a more moderate decrease of anabolism althought it stimulates strongly the production of NO, suggesting that this radical is an important bût not an exclusive mediator in the loss of proteoglycan synthesis. The superoxide anion constitutes in fact a key regulator of the NO effects in cartilage. So IL-1 and IL-17 can be differentiated by their capacity to generate peroxynitrite which could inhibit a key enzyme involved in the synthesis of proteoglycans, glucuronosyltransferase I. Besides, a kinetics of IL-1 effects in cartilage showed that the loss of anabolism observed at 48 hrs is followed by an increase at 96 hrs. The analysis of genes expression indicates that proteins as iNOS and IL-1 are strongly induced in early phases. On the contrary, the decrease IGF-1 expression could explain the inhibition of the proteoglycans synthesis.
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http://docnum.univ-lorraine.fr/prive/SCD_T_2003_0240_PACQUELET.pdf
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https://hal.univ-lorraine.fr/tel-01746929
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Submitted on : Thursday, March 29, 2018 - 10:47:57 AM
Last modification on : Wednesday, October 14, 2020 - 4:08:40 AM

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Sandrine Pacquelet. Rôle et mécanisme d'action de 2 cytokines pro-inflammatoires, interleukine-1B et interleukine-17, dans la dégénérescence du cartilage au cours des arthropathies. Biologie cellulaire. Université Henri Poincaré - Nancy 1, 2003. Français. ⟨NNT : 2003NAN11301⟩. ⟨tel-01746929⟩

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