Quantitative analysis of cytokine gene expression in rheumatoid arthritis.
Quantitative analysis of cytokine gene expression in rheumatoid arthritis.
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DOI：
10.4049/jimmunol.145.3.1037
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发表时间：
1990-05
影响因子：
4.4
通讯作者：
G. Firestein;J. Álvaro-Gracia;R. Maki
中科院分区：
文献类型：
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作者：
G. Firestein;J. Álvaro-Gracia;R. Maki
以往对类风湿性关节炎（RA）细胞因子谱的研究主要局限于通过生物学或免疫学测定评估滑液（SF）或滑膜组织（ST）中这些介质的水平。我们通过SF细胞、酶促分散的ST细胞和ST冰冻切片的原位杂交研究了RA中细胞因子基因的表达。研究了RA ST细胞（n = 7），并且高百分比的细胞与以下反义探针杂交：IL-6 = 19 +/- 3.3%，IL-1 β = 9.9 +/- 1.7%，IL-1 β = 19 +/- 1.7%，IL-1 β = 19 +/- 1.7%。TNF-alpha = 5.8 +/- 1.4%;粒细胞-巨噬细胞-CSF = 2.2 +/- 0.8%;转化生长因子-β 1 = 1.3 +/- 0.2%（与有义探针相比，每种探针的p均小于0.05）。使用骨关节炎ST细胞也发现了类似的结果，尽管与RA相比，骨关节炎中表达IL-6基因的细胞百分比（7.1 +/- 2.5%）显著较少。RA ST细胞没有显着结合IFN-γ探针（0.2 +/- 0.1%阳性），尽管如果用PHA刺激，它们能够表达IFN-γ基因。ST细胞的OKM 1+群体（即，巨噬细胞谱系细胞）中IL-1 β和TNF-α大量富集，而OKM 1群（淋巴细胞、成纤维细胞和B型滑膜细胞）中IL-6富集。绝大多数表达IL-6基因的细胞是非T细胞。此外，与RA ST冷冻切片的杂交将IL-6 mRNA定位于滑膜衬里层，其由A型和B型滑膜细胞组成。与ST中观察到的细胞因子基因表达的高水平相反，SF细胞没有与任何细胞因子探针显著杂交。如果用LPS或PHA刺激，SF细胞分别表达IL-1 β或IFN-γ基因。
Previous studies of the cytokine profile of rheumatoid arthritis (RA) have been primarily limited to the assessment of the levels of these mediators in synovial fluid (SF) or synovial tissues (ST) by biologic or immunologic assays. We have studied cytokine gene expression in RA by in situ hybridization of SF cells, enzymatically dispersed ST cells, and frozen sections of ST. RA ST cells (n = 7) were studied and a high percentage of cells hybridized to the following anti-sense probes: IL-6 = 19 +/- 3.3%; IL-1 beta = 9.9 +/- 1.7%; TNF-alpha = 5.8 +/- 1.4%; granulocyte-macrophage-CSF = 2.2 +/- 0.8%; transforming growth factor-beta 1 = 1.3 +/- 0.2% (p less than 0.05 for each compared to sense probes). Similar results were found using osteoarthritis ST cells, although the percentage of cells expressing the IL-6 gene (7.1 +/- 2.5%) was significantly less in osteoarthritis compared to RA. RA ST cells did not significantly bind the IFN-gamma probe (0.2 +/- 0.1% positive), although they were capable of expressing the IFN-gamma gene if stimulated with PHA. The OKM1+ population of ST cells (i.e., macrophage lineage cells) was greatly enriched for IL-1 beta and TNF-alpha, whereas the OKM1- population (lymphocytes, fibroblasts, and type B synoviocytes) was enriched for IL-6. The vast majority of cells expressing the IL-6 gene were non-T cells. Furthermore, hybridization to RA ST frozen sections localized IL-6 mRNA to the synovial lining layer, which is comprised of type A and type B synoviocytes. In contrast to the high level of cytokine gene expression observed in ST, SF cells did not hybridize significantly to any of the cytokine probes. If stimulated with LPS or PHA, SF cells expressed IL-1 beta or IFN-gamma genes, respectively.