Handel M L, McMorrow L B, Gravallese E M
Harvard School of Public Health, Boston, Massachusetts, USA.
Arthritis Rheum. 1995 Dec;38(12):1762-70. doi: 10.1002/art.1780381209.
To identify the cells that express transcription factor NF-kappa B subunits p50 and p65 in synovial tissue from patients with rheumatoid arthritis (RA) and to correlate the distribution of p50 and p65 with CD14 (macrophage lipopolysaccharide receptor) and members of the AP-1 transcription factor family, Jun and Fos.
Immunohistochemistry was used to identify p50, p65, Jun and Fos in sections of synovial tissue from 13 patients with RA and 4 "normal" control subjects. Double staining for CD14 and each of the transcription factor subunits was performed.
Subunits p50 and p65 were present in the nuclei of synovial cells in all 13 RA patients, with expression varying from rare cells to more than half of all cells. In most cases, nuclear p50 and p65 were present in approximately one-third of synovial lining cells and in a variable proportion of cells scattered throughout the sublining region, including the endothelium. The distributions of p50 and p65 were similar. Jun and Fos were present in the nuclei of a large proportion of synovial lining cells with significantly less expression elsewhere. In each case the Jun/Fos distribution was clearly different from the p50/p65 distribution, although there was significant overlap in many cases. Cells expressing CD14 were mostly Jun/Fos negative and were predominantly p50/p65 positive. There was negligible staining for p50 or p65 in the 4 normal control synovium samples.
In most RA patients, the p50 and p65 subunits of NF-kappa B were present in the majority of CD14-positive cells within the lining and sublining regions and in a proportion of other cells throughout the synovium, including endothelial cells. NF-kappa B is likely to play an important role in the expression of macrophage-derived cytokines in rheumatoid synovium. Different but overlapping distributions of nuclear p50 and p65 versus Jun and Fos indicate separate or divergent mechanisms for the activation of NF-kappa B and the expression of AP-1 proteins in rheumatoid synovium.
鉴定类风湿关节炎（RA）患者滑膜组织中表达转录因子核因子-κB（NF-κB）亚基p50和p65的细胞，并将p50和p65的分布与CD14（巨噬细胞脂多糖受体）以及AP-1转录因子家族成员Jun和Fos进行关联分析。
采用免疫组织化学方法，对13例RA患者和4例“正常”对照者的滑膜组织切片进行p50、p65、Jun和Fos的鉴定。同时进行CD14与各转录因子亚基的双重染色。
在所有13例RA患者中，p50和p65亚基均存在于滑膜细胞核中，表达情况从少数细胞到超过半数细胞不等。在大多数情况下，核内p50和p65存在于约三分之一的滑膜衬里细胞中，以及分布于整个滑膜下层区域（包括内皮细胞）的不同比例的散在细胞中。p50和p65的分布相似。Jun和Fos存在于大部分滑膜衬里细胞核中，在其他部位表达明显较少。在每种情况下，Jun/Fos的分布与p50/p65的分布明显不同，尽管在许多情况下存在显著重叠。表达CD14的细胞大多为Jun/Fos阴性，主要为p50/p65阳性。在4例正常对照滑膜样本中，p50或p65的染色可忽略不计。
在大多数RA患者中，NF-κB的p50和p65亚基存在于衬里和下层区域的大多数CD14阳性细胞以及滑膜内其他部分细胞（包括内皮细胞）中。NF-κB可能在类风湿滑膜中巨噬细胞源性细胞因子的表达中起重要作用。核内p50和p65与Jun和Fos不同但有重叠的分布表明，在类风湿滑膜中NF-κB的激活和AP-1蛋白的表达存在不同或不同的机制。
