MODULATION OF HUMAN CHONDROCYTE METABOLISM BY RECOMBINANT HUMAN INTERFERON-GAMMA - INVITRO EFFECTS ON BASAL AND IL-1-STIMULATED PROTEINASE PRODUCTION, CARTILAGE DEGRADATION AND DNA-SYNTHESIS

MODULATION OF HUMAN CHONDROCYTE METABOLISM BY RECOMBINANT HUMAN INTERFERON-GAMMA - INVITRO EFFECTS ON BASAL AND IL-1-STIMULATED PROTEINASE PRODUCTION, CARTILAGE DEGRADATION AND DNA-SYNTHESIS
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DOI:
10.1016/0167-4889(89)90085-2
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发表时间:
1989-07-11
期刊:
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子:
--
通讯作者:
RUSSELL, RGG
RUSSELL, RGG
中科院分区:
其他
文献类型:
--
作者:
ANDREWS, HJ;BUNNING, RAD;RUSSELL, RGG

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用重组人干扰素γ (IFN-. γ)单独或联合白细胞介素1 (IL-1)治疗单层培养的人关节软骨细胞和人关节软骨碎片。干扰素可以利用。单独抑制金属蛋白酶的产生,如酪蛋白酶测定,并减少培养软骨碎片的糖胺聚糖释放。DNA的合成,通过[3H]胸腺嘧啶掺入来测量,是由IFN-. γ刺激的。IL-1的存在也有类似的效果。因此,干扰素可以利用。反对IL-1对酪蛋白酶产生的刺激作用,并减少IL-1刺激的软骨降解,通过糖胺聚糖释放来测量。相反,IFN-。对IL-1刺激的前列腺素生成无影响,与IL-1协同作用,对DNA合成产生较大刺激。这些结果表明IFN-。在体外对关节软骨细胞有许多影响,并提示IFN- γ可能起作用。在炎性关节条件下限制软骨退化。
Human articular chondrocytes in monolayer culture and fragments of human articular cartilage were treated with recombinant human interferon gamma (IFN-.gamma.) both alone and in combination with interleukin 1 (IL-1). IFN-.gamma. alone inhibits metalloproteinase production, as measured in the caseinase assay, and decreases glycosaminoglycan release from cartilage fragments in culture. The synthesis of DNA, as measured by [3H]thymidine incorporation, is stimulated by IFN-.gamma.. Similar effects are seen in the presence of IL-1. Thus, IFN-.gamma. opposes the stimulatory effect of IL-1 on caseinase production and decreases IL-1-stimulated cartilage degradation, as measured by glycosaminoglycan release. In contrast, IFN-.gamma. has no effect on IL-1-stimulated prostaglandin production, and acts synergistically with IL-1 to cause a large stimulation of DNA synthesis. These results show that IFN-.gamma. has a number of effects on articular chondrocytes in-vitro and suggest a possible role for IFN-.gamma. in limiting cartilage degradation in inflammatory joint conditions.