Zhang Yan-Bei, He Feng-Lian, Fang Ming, Hua Tian-Feng, Hu Bi-Dan, Zhang Zhi-Hong, Cao Qi, Liu Rong-Yu
Department of Respiratory Medicine, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People's Republic of China.
Mol Biol Rep. 2009 Jul;36(6):1475-81. doi: 10.1007/s11033-008-9338-9. Epub 2008 Sep 2.
It has been reported lately that Toll-like receptors (TLRs) play an essential role in the activation of innate immunity, and TLRs are expressed in a large number of immune cells like B-lymphocytes, monocytes, plasmacytoid dendritic cells and at low levels in human respiratory cells as well as epithelial cells. In the present study, we investigated whether there is a relationship between the expression of TLR4 or TLR9 and the clinical or pathological changes in human lung cancer.
Protein expression of TLR4 and TLR9 was assessed by using immunohistochemistry and western blotting. mRNA expressions of TLR4 and TLR9 were detected by reverse transcriptase polymerase chain reaction (RT-PCR).
High TLR4 and TLR9 mRNA signal intensity was found in the majority of lung cancer specimens. In contrast, tumor-free lung tissue showed lower signal intensity. Consistently, the low amount of TLR4 and TLR9 protein expression was found in tumor-free lung tissue, while they were strongly expressed in lung cancer tissue. In addition, we found for the first time that the differentiation degree of tumor cells was positively correlated with the expression level of TLR4. There was no relationship between the expressions of TLR4 or TLR9 and patients' age, gender, smoking, the histological type of tumor, lymph node metastasis, and tumor node metastases (TNM) stage.
We found that both mRNA and protein levels of TLR4 and TLR9 were strongly expressed in lung cancer tissue. In addition, we reported for the first time a positive correlation between the expression level of TLR4 and malignancy of lung cancer. These results suggested that TLR4 and TLR9 may be involved in the development of lung cancer which may have the potentials for the treatment of this malignant tumor.
最近有报道称，Toll样受体（TLRs）在先天免疫激活中起关键作用，TLRs在大量免疫细胞如B淋巴细胞、单核细胞、浆细胞样树突状细胞中表达，在人类呼吸道细胞以及上皮细胞中也有低水平表达。在本研究中，我们调查了TLR4或TLR9的表达与人类肺癌临床或病理变化之间是否存在关联。
采用免疫组织化学和蛋白质印迹法评估TLR4和TLR9的蛋白表达。通过逆转录聚合酶链反应（RT-PCR）检测TLR4和TLR9的mRNA表达。
在大多数肺癌标本中发现TLR4和TLR9 mRNA信号强度较高。相比之下，无肿瘤肺组织的信号强度较低。同样，在无肿瘤肺组织中发现TLR4和TLR9蛋白表达量较低，而它们在肺癌组织中强烈表达。此外，我们首次发现肿瘤细胞的分化程度与TLR4的表达水平呈正相关。TLR4或TLR9的表达与患者的年龄、性别、吸烟情况、肿瘤组织学类型、淋巴结转移及肿瘤淋巴结转移（TNM）分期之间均无关联。
我们发现肺癌组织中TLR4和TLR9的mRNA及蛋白水平均强烈表达。此外，我们首次报道了TLR4的表达水平与肺癌恶性程度之间呈正相关。这些结果表明，TLR4和TLR9可能参与肺癌的发生发展，这可能为该恶性肿瘤的治疗提供潜在靶点。
