NF-kappaB, p38 MAPK and JNK are highly expressed and active in the stroma of human colonic adenomatous polyps
NF-kappaB, p38 MAPK and JNK are highly expressed and active in the stroma of human colonic adenomatous polyps
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DOI：
10.1038/sj.onc.1204162
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发表时间：
2001-02-15
期刊：
影响因子：
8
通讯作者：
Peppelenbosch, MP
中科院分区：
文献类型：
--
作者：
Hardwick, JCH;van den Brink, GR;Peppelenbosch, MP
控制结肠腺瘤性息肉进展为结肠癌的因素尚不清楚。 NSAIDs 作为化学预防剂并缩小结肠息肉的大小的观察表明炎症信号传导的参与，但尚未研究结肠息肉中的炎症信号传导。我们使用具有激活特异性抗体的免疫组织化学方法研究了人结肠腺瘤中 NF-kappaB、JNK 和 p38 MAPK 活性形式的表达，我们发现活性 NF-kappaB 见于也表达 COX-2 和 TNF-α 的基质巨噬细胞中，活性 JNK 见于基质和上皮内 T 淋巴细胞以及新血管周围皮细胞中，活性 p38 MAPK 最高在巨噬细胞和其他基质细胞中表达。这些结果证明结肠息肉中存在活跃的炎症信号转导，并且这些信号转导主要位于间质中。就 NF-κB 而言，这与 COX-2 的细胞定位一致。这些结果支持了非甾体抗炎药可能通过作用于基质细胞而不是上皮细胞来发挥作用的证据。
The factors that govern the progression from colonic adenomatous polyp to colon cancer are poorly understood. The observation that NSAIDs act as chemopreventative agents and reduce the size of colonic polyps suggests the involvement of inflammatory signalling, but inflammatory signalling in colonic polyps has not been studied. We investigated the expression of the active forms of NF-kappaB, JNK and p38 MAPK using immunohistochemistry with activation specific antibodies in human colonic adenomas, We show that active NF-kappaB is seen in stromal macrophages that also express COX-2 and TNF-alpha, active JNK is seen in stromal and intraepithelial T-lymphocytes and periendothelial cells of new blood vessels, and active p38 MAPK is most highly expressed in macrophages and other stromal cells. These results demonstrate the presence of active inflammatory signal transduction in colonic polyps and that these are predominantly in the stroma, In the case of NF-kappaB this coincides with the cellular localisation of COX-2. These results support evidence that NSAIDs may act through effects on stromal cells rather than epithelial cells.