Expression and significance of HMGB1, TLR4 and NF-κB p65 in human epidermal tumors.
Expression and significance of HMGB1, TLR4 and NF-κB p65 in human epidermal tumors.
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DOI：
10.1186/1471-2407-13-311
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发表时间：
2013-06-26
期刊：
影响因子：
3.8
通讯作者：
Gong F
中科院分区：
文献类型：
--
作者：
Weng H;Deng Y;Xie Y;Liu H;Gong F
高迁移率族蛋白盒 1 (HMGB1) 是一种位于细胞核中的 DNA 结合蛋白。它被释放到细胞外液中，作为一种新型促炎细胞因子与 Toll 样受体 4 (TLR4) 相互作用，激活核因子 -κB (NF-κB)。这一系列事件涉及肿瘤的生长和进展。然而，HMGB1、TLR4和NF-κB对表皮肿瘤的影响仍不清楚。人类表皮肿瘤标本取自 96 名患者。采用免疫组织化学法检测人表皮肿瘤和正常皮肤标本中HMGB1、TLR4和NF-κB p65的表达。采用Western blot方法检测人表皮肿瘤及正常组织中上皮细胞核中NF-κB p65的表达情况。免疫组织化学和蛋白质印迹分析表明，良性脂溢性角化病（SK）、癌前病变（PCL）、低度恶性基底细胞癌（BCC）和高度恶性鳞状细胞癌（SCC）上皮细胞核中p65表达呈进行性但具有统计学意义的显着增加（P <0.01）。 SK细胞外HMGB1水平显着高于正常皮肤（NS）（P <0.01），也高于SCC，但无统计学意义。 SCC细胞上皮膜上TLR4的水平显着高于SK、PCL、BCC和NS（P <0.01）。上皮细胞核p65表达量与上皮细胞膜TLR4表达量呈显着正相关（r = 0.3212，P<0.01）。这些发现表明炎症随着恶性肿瘤的增加而加剧。他们还表明，TLR4 信号通路（而不是 HMGB1）可能是高级恶性表皮肿瘤炎症的主要介质。联合检测上皮细胞核中的p65和上皮细胞膜上的TLR4可能有助于表皮恶性肿瘤的准确诊断。
High mobility group protein box 1 (HMGB1) is a DNA binding protein located in nucleus. It is released into extracellular fluid where it acts as a novel proinflammatory cytokine which interacts with Toll like receptor 4 (TLR4) to activate nuclear factor-κB (NF-κB). This sequence of events is involved in tumor growth and progression. However, the effects of HMGB1, TLR4 and NF-κB on epidermal tumors remain unclear. Human epidermal tumor specimens were obtained from 96 patients. Immunohistochemistry was used to detect expression of HMGB1, TLR4 and NF-κB p65 in human epidermal tumor and normal skin specimens. Western blot analysis was used to detect the expression of NF-κB p65 in epithelial cell nuclei in human epidermal tumor and normal tissues. Immunohistochemistry and western blot analysis indicated a progressive but statistically significant increase in p65 expression in epithelial nuclei in benign seborrheic keratosis (SK), precancerous lesions (PCL), low malignancy basal cell carcinoma (BCC) and high malignancy squamous cell carcinoma (SCC) (P <0.01). The level of extracellular HMGB1 in SK was significantly higher than in normal skin (NS) (P <0.01), and was higher than in SCC but without statistical significance. The level of TLR4 on epithelial membranes of SCC cells was significantly higher than in SK, PCL, BCC and NS (P <0.01). There was a significant positive correlation between p65 expression in the epithelial nuclei and TLR4 expression on the epithelial cell membranes (r = 0.3212, P <0.01). These findings indicate that inflammation is intensified in parallel with increasing malignancy. They also indicate that the TLR4 signaling pathway, rather than HMGB1, may be the principal mediator of inflammation in high-grade malignant epidermal tumors. Combined detection of p65 in the epithelial nuclei and TLR4 on the epithelial membranes may assist the accurate diagnosis of malignant epidermal tumors.
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影响因子：
11.2
作者：
Jube S;Rivera ZS;Bianchi ME;Powers A;Wang E;Pagano I;Pass HI;Gaudino G;Carbone M;Yang H
通讯作者：
Yang H
影响因子：
64.5
作者：
HASHIMOTO, C;HUDSON, KL;ANDERSON, KV
通讯作者：
ANDERSON, KV
影响因子：
4.8
作者：
Dai, Shipan;Sodhi, Chhinder;Hackam, David J.
通讯作者：
Hackam, David J.
DOI：
10.4049/jimmunol.1102157
发表时间：
2012-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bauerfeld CP;Rastogi R;Pirockinaite G;Lee I;Hüttemann M;Monks B;Birnbaum MJ;Franchi L;Nuñez G;Samavati L
通讯作者：
Samavati L
影响因子：
33.6
作者：
Peek RM Jr;Fiske C;Wilson KT
通讯作者：
Wilson KT