MODULATION BY INTERLEUKIN-1 AND TUMOR NECROSIS FACTOR-ALPHA OF PRODUCTION OF COLLAGENASE, TISSUE INHIBITOR OF METALLOPROTEINASES AND COLLAGEN TYPES IN DIFFERENTIATED AND DEDIFFERENTIATED ARTICULAR CHONDROCYTES
MODULATION BY INTERLEUKIN-1 AND TUMOR NECROSIS FACTOR-ALPHA OF PRODUCTION OF COLLAGENASE, TISSUE INHIBITOR OF METALLOPROTEINASES AND COLLAGEN TYPES IN DIFFERENTIATED AND DEDIFFERENTIATED ARTICULAR CHONDROCYTES
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DOI：
10.1016/0167-4889(90)90145-4
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发表时间：
1990-05-22
期刊：
影响因子：
--
通讯作者：
VAES, G
中科院分区：
文献类型：
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作者：
LEFEBVRE, V;PEETERSJORIS, C;VAES, G
白介素1和肿瘤坏死因子α的作用。(TNF.Alpha)通过比较原代培养中分化的软骨细胞和传代后期的去分化细胞对重组人IL-1α、hr-TNF.α的反应，研究了兔关节软骨细胞胶原代谢的几个参数。和兔巨噬细胞条件培养液中富含细胞因子的部分。作为对IL1或TNF.α的反应，分化的软骨细胞(即产生软骨特异的II型和XI型胶原，但不产生I型胶原)急剧减少其胶原的合成，这种减少涉及II型和XI型胶原，而不是持续地改变它们产生的非胶原蛋白；它们还将较小比例的胶原结合到基质中。对于hr-IL.Alpha，也获得了类似水平的反应。在皮摩尔和hr-TNF.α。以纳摩尔浓度。然而，只有在血清存在的情况下，才能表现出肿瘤坏死因子α的作用，而不是IL1的作用。同时，IL1诱导软骨细胞产生前胶原酶(这与两种细胞因子诱导滑膜成纤维细胞和皮肤成纤维细胞产生类似水平的原胶原酶不同)，但两种细胞因子都不影响胶原酶抑制物TIMP的积累。这些作用不受消炎痛的影响，因此不太可能是由前列腺素介导的。在单层传代培养过程中，软骨细胞对IL1和TNF.α的前胶原酶活性更加敏感，但对TNF.低于IL1。他们还增加了TIMP的产生，而TIMP仍然不受细胞因子的影响。同时，它们减少了胶原的产生，并逐渐取代了成纤维细胞特异性胶原的合成，I型、III型和V型取代了II型和XI型。作用于去分化细胞，即使在吲哚美辛、IL1和TNF.α存在的情况下也是如此。进一步减少了胶原的合成，减少了典型的I型(即α(I)2)cNTDot的产生。α2(I)分子)和V型胶原以及它们在基质中的结合，但增加III型胶原的合成。因此，不仅是IL1，而且还有TNF.Alpha。可以对关节软骨病理过程中发生的胶原降解和修复过程产生深远的影响。
The actions of interleukin 1 (IL1) and tumor necrosis factor .alpha. (TNF.alpha.) on several parameters of the collagen metabolism of rabbit articular chondrocytes were studied by comparing the responses of either differentiated chondrocytes in primoculture or dedifferentiated cells in late passage culture to human recombinant (hr) IL1.alpha., hr-TNF.alpha. and cytokine-enriched fractions of rabbit macrophage-conditioned media. In response to IL1 or TNF.alpha., differentiated chondrocytes (i.e., producing the cartilage-specific collagens, types II and XI, but not type I), sharply reduced their synthesis of collagen, a reduction which involved both types II and XI collagens, without consistently changing their production of non-collagenous proteins; they also incorporated a smaller proportion of collagen into the matrix. Similar levels of response were obtained for hr-IL.alpha. at picomolar and for hr-TNF.alpha. at nanomolar concentrations. However, the action of TNF.alpha., but not of IL1, was manifested only in the presence of serum. Simultaneously, IL1, but not TNF.alpha., induced the chondrocyte production of of procollagenase (a difference which contrasted with the similar levels of procollagenase induced by both cytokines in synovial and skin fibroblasts) but neither cytokine influenced the accumulation of the collagenase inhibitor TIMP. These effects were not affected by indomethacin and are thus unlikely to be prostaglandin-mediated. During their dedifferentiation in monolayer subcultures, chondrocytes became more sensitive to the procollagenase ability of IL1 and TNF.alpha., but their response to TNF.alpha. was lower than to IL1. They also increased their production of TIMP, which remained unaffected by the cytokines. Simultaneously, they decreased their production of collagen and substituted progressively the synthesis of fibroblast-specific collagens, types I, III and V, for types II and XI. Acting on dedifferentiated cells, even in the presence of indomethacin, IL1 and TNF.alpha. further decreased the synthesis of collagen, reducing the production of both typical type I (i.e. .alpha.(I)2 .cntdot. .alpha.2(I) molecules) and type V collagens as well as their incorporation into the matrix, but increasing the synthesis of type III collagen. Therefore not only IL1, but also TNF.alpha. can exert profound influences on the collagen degradation and repair processes occurring in the pathology of articular cartilage.