INTERLEUKIN-1 SUPPRESSES EXPRESSION OF CARTILAGE-SPECIFIC TYPE-II AND TYPE-IX COLLAGENS AND INCREASES TYPE-I AND TYPE-III COLLAGENS IN HUMAN CHONDROCYTES
INTERLEUKIN-1 SUPPRESSES EXPRESSION OF CARTILAGE-SPECIFIC TYPE-II AND TYPE-IX COLLAGENS AND INCREASES TYPE-I AND TYPE-III COLLAGENS IN HUMAN CHONDROCYTES
复制标题
DOI：
10.1172/jci113823
复制
发表时间：
1988-12-01
影响因子：
15.9
通讯作者：
KRANE, SM
中科院分区：
文献类型：
--
作者：
GOLDRING, MB;BIRKHEAD, J;KRANE, SM
在炎症性疾病中，如类风湿性关节炎，时间细胞的功能，包括基质蛋白和蛋白酶的合成，通过与浸润性血管膜细胞的相互作用而改变。IL-1是单核炎性细胞的主要分泌产物之一。在本研究中我们发现重组人IL-1β。抑制培养的人肋骨软骨细胞合成软骨特异性II型胶原，并伴随α1(II)和α1(IX)前胶原mRNAs的稳定水平下降。相反，IL-1增加了I型和III型胶原的合成以及α1(I)、α2(I)和α1(III)前胶原mRNAs的水平，正如我们之前使用人类关节软骨细胞和滑膜成纤维细胞所描述的那样。只有当IL-1刺激的PGE2合成被环氧合酶抑制剂吲哚美辛阻断时，才能观察到IL-1的这种刺激作用。IL-1单独抑制II型胶原mRNA水平并不是由于IL-1刺激PGE2，因为加入消炎痛并不能逆转这种抑制，而是实际上增强了这种抑制。从培养第2天开始，将新鲜分离的软骨细胞持续暴露在接近最大浓度的IL-1(2.5 PM)中，可完全抑制II型胶原mRNA的水平，增加I型和II型胶原mRNAs的水平，从而在第7天逆转α1(II)/α1(I)前胶原mRNAs的比例。因此，IL-1可以在翻译前水平改变软骨中合成的不同类型胶原的相对量，从而可能导致炎症条件下软骨基质的不适当修复。
In inflammatory diseases such as rheumatoid arthritis, functions of chrondrocytes including synthesis of matrix proteins and proteinases are altered through interactions with cells of the infiltrating pannus. One of the major secreted products of mononuclear inflammatory cells is IL-1. In this study we found that recombinant human IL-1.beta. suppressed synthesis of cartilage-specific type II collagen by cultured human costal chondrocytes associated with decreased steady state levels of .alpha.1 (II) and .alpha.1(IX) procollagen mRNAs. In contrast, IL-1 increased syntehsis of types I and III collagens and levels of .alpha.1(I), .alpha.2(I), and .alpha.1(III) procollagen mRNAs, as we described previously using human articular chondrocytes and synovial fibroblasts. This stimulatory effect of IL-1 was observed only when IL-1-stimulated PGE2 synthesis was blocked by the cyclooxygenase inhibitor indomethacin. The suppression of type II collagen mRNA levels by Il-1 alone was not due to IL-1 stimulated PGE2, since addition of indomethacin did not reverse, but actually potentiated, this inhibition. Continuous exposure of freshly isolated chondrocytes from day 2 of culture to approximately half-maximal concentrations of IL-1 (2.5 pM) completely suppressed levels of type II collagen mRNA and increased levels of types I and II collagen MRNAs, thereby reversing the ratio of .alpha.1(II)/.alpha.1(I) procollagen mRNAs from > 6.0 to < 1.0 by day 7. IL-1, therefore, can modify, at a pretranslational levels, the relative amounts of the different types of collagen synthesized in cartilage and thereby could be responsible for the inappropriate repair of cartilage matrix in inflammatory conditions.