AIM: To identify the mechanisms of chemokine ligand 20(CCL20)-induced hepatocellular carcinoma(HCC) metastasis and evaluate it as a prognostic marker. METHODS: Expression of CCL20 was evaluated by immunohistochemistry...AIM: To identify the mechanisms of chemokine ligand 20(CCL20)-induced hepatocellular carcinoma(HCC) metastasis and evaluate it as a prognostic marker. METHODS: Expression of CCL20 was evaluated by immunohistochemistry in HCC tissues from 62 patients who underwent curative resection. The relationship between CCL20 expression and clinicopathologic features was analyzed. Univariate and multivariate analyses were performed to evaluate its predictive value for recurrence and survival of HCC patients. The expression levels ofepithelial-mesenchymal transition(EMT)-and signaling pathway-related proteins were evaluated by Western blotting and immunocytochemistry. The effects of CCL20 on HCC cell proliferation and migration were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenoltetrazolium bromide(MTT) and Transwell assays. RESULTS: CCL20 immunoreactivity was detected in all 62 patient specimens. CCL20 expression was associated with preoperative alpha-fetoprotein level(P = 0.043), tumor size(P = 0.000), tumor number(P = 0.008), vascular invasion(P = 0.014), and tumor differentiation(P = 0.007). Patients with high CCL20 expression had poorer recurrence-free and overall survivals compared to those with low CCL20 expression(both P < 0.001). CCL20 induced EMT-like changes in HCC cells and increased their proliferation and migration ability(P < 0.05). Western blotting and immunofluorescence staining showed that CCL20 induced an EMT-like phenotype in HCC cells, and increased expression of phosphorylated AKT, β-catenin and vimentin, and decreased E-cadherin expression(P < 0.05). The correlation analysis revealed that high CCL20 expression in HCC tissue specimens was negatively correlated with E-cadherin expression(13.33%, 4/30), and positively correlated with vimentin(90.0%, 27/30), β-catenin(96.67%, 29/30) and p-AKT(76.67%, 23/30) expression.CONCLUSION: CCL20 expression is associated with HCC recurrence and patient survival and promotes HCC cell proliferation and migration by inducing EMT-like changes via PI3K/AKT and Wnt/β-catenin pathways.展开更多
Summary: In order to explore the possible role of CC chemokine ligand 20 (CCL20) and its receptor CC chemokine receptor 6 (CCR6) in the pathogenesis of psoriasis, the expression levels of mRNA of them in psoriatic les...Summary: In order to explore the possible role of CC chemokine ligand 20 (CCL20) and its receptor CC chemokine receptor 6 (CCR6) in the pathogenesis of psoriasis, the expression levels of mRNA of them in psoriatic lesions were investigated. The skin biopsies were collected from skin lesions in 35 cases of psoriasis vulgaris and 18 normal controls. RT-PCR was used to semi-quantitatively analyze the mRNA expression of CCL20 and CCR6 in the psoriatic lesions and the normal skin tissues. The results showed that the mRNA of CCL20 and CCR6 was present in every specimen. The expression levels of CCL20 mRNA in skin lesions were 1.1397±0.0521, which were greatly higher than those in normal controls (0.8681±0.0308) (P<0.001). The expression levels of CCR6 mRNA in skin lesions were 1.1103±0.0538, significantly higher than in the controls (0.9131±0.0433, P<0.001). These findings indicate that up-regulated expression of CCL20 and CCR6 mRNA might be related to the pathogenesis of psoriasis.展开更多
Chemokines belong to a superfamily of small, cytokinelike proteins, which induce multiple physiological functions, particularly cytoskeletal rearrangement and compartment-specific migration through their interaction w...Chemokines belong to a superfamily of small, cytokinelike proteins, which induce multiple physiological functions, particularly cytoskeletal rearrangement and compartment-specific migration through their interaction with G-protein-coupled receptors. Chemokines and their receptors have been widely acknowledged as essential and selective mediators in leukocyte migration in inflammatory response. It is now established that the chemokine/chemokine receptor system is also used by cancer cells to direct lymphatic and haematogenous spreading and additionally has an impact on the site of metastatic growth of different tumours. In recent years an increasing number of studies have drawn attention to CC-chemokine cysteine motif chemokine ligand 20(CCL20) and its physiological sole receptor CCR6 to play a role in the onset, development and metastatic spread of various gastrointestinal cancer entities. Among various cancer types CCR6 was also demonstrated to be significantly overexpressed in colorectal cancer(CRC) and stimulation by its physiological ligand CCL20 has been reported to promote CRC cell proliferation and migration in vitro. Further, the CCL20/CCR6 system apparently plays a role in the organ-selective liver metastasis of CRC. Here we review the literature on expression patterns of CCL20 and CCR6 and their physiological interactions as well as the currently presumed role of CCL20 and CCR6 in the formation of CRC and the development of liver metastasis, providing a potential basis for novel treatment strategies.展开更多
目的探讨血清CC趋化因子配体20(CCL20)及白介素-17(IL-17)水平与子痫前期的相关性及其对子痫前期的诊断效能。方法选择2021年1月至2022年12月陕西省人民医院产科收治的150例子痫前期孕妇为子痫前期组,另选取同期90例健康妊娠妇女为对照...目的探讨血清CC趋化因子配体20(CCL20)及白介素-17(IL-17)水平与子痫前期的相关性及其对子痫前期的诊断效能。方法选择2021年1月至2022年12月陕西省人民医院产科收治的150例子痫前期孕妇为子痫前期组,另选取同期90例健康妊娠妇女为对照组。采用酶联免疫吸附法(ELISA)检测血清CCL20及IL-17的表达水平,采用Pearson相关法分析血清CCL20及IL-17与子痫前期患者临床参数的相关性;采用受试者工作特征曲线(ROC)分析血清CCL20及IL-17对子痫前期的诊断价值。结果子痫前期组孕妇血清CCL20及IL-17水平均显著高于对照组(P<0.001)。子痫前期组孕妇血清CCL20及IL-17的表达均与收缩压(分别为r=0.463、r=0.545)、舒张压(分别为r=0.475、r=0.467)及尿蛋白(分别为r=0.302、r=0.342)呈显著正相关(P<0.001),而与终止妊娠孕周(分别为r=-0.281、r=-0.188)、新生儿出生体重(分别为r=-0.299、r=-0.200)及1 min Apgar评分(分别为r=-0.215、r=-0.194)呈显著负相关(P<0.05)。子痫前期组孕妇血清CCL20与IL-17水平呈显著正相关(r=0.615,P<0.001)。血清CCL20及IL-17诊断子痫前期的临界值分别为50.025 pg/ml及48.825 pg/ml,血清CCL20+IL-17联合诊断子痫前期的曲线下面积最大,灵敏度及特异度分别为87.3%及94.4%。结论子痫前期孕妇血清CCL20及IL-17的水平显著高于健康孕妇,且CCL20及IL-17水平与患者的血压、尿蛋白、妊娠结局及新生儿情况均存在显著相关性,两指标联合应用对子痫前期有一定的诊断价值。展开更多
目的:观察凉血解毒汤对银屑病小鼠皮肤组织中CC趋化因子配体20(CCL20)/CC趋化因子受体6(CCR6)表达的干预作用。方法:24只BALB/c雄性小鼠随机分为空白对照组、银屑病模型组、凉血解毒汤中药治疗组和趋化因子CCL20单克隆抗体(阳性药)治疗...目的:观察凉血解毒汤对银屑病小鼠皮肤组织中CC趋化因子配体20(CCL20)/CC趋化因子受体6(CCR6)表达的干预作用。方法:24只BALB/c雄性小鼠随机分为空白对照组、银屑病模型组、凉血解毒汤中药治疗组和趋化因子CCL20单克隆抗体(阳性药)治疗组。用咪喹莫特诱导小鼠银屑病模型,采用银屑病皮损面积和疾病严重程度(psoriasis area and severity index,PASI)评分标准观察银屑病样小鼠皮损的变化情况。光镜下观察皮损组织形态学变化,测量表皮层厚度。采用real-time PCR检小鼠皮肤组织样本中CCL20和CCR6表达的变化。结果:银屑病模型组小鼠皮肤出现大量鳞屑和红斑,表皮增厚;与银屑病模型组小鼠比较,凉血解毒汤组小鼠银屑病样皮损程度较轻,红斑、鳞屑以及表皮增厚程度轻于模型组,PASI分数降低,皮肤组织CCL20以及CCR6的表达明显低于模型组。趋化因子CCL20单克隆抗体治疗组小鼠银屑病皮损程度较轻,红斑、鳞屑以及表皮增厚程度轻于模型组,PASI分数降低,皮肤组织CCL20以及CCR6的表达明显低于模型组。结论:凉血解毒汤可能通过下调CCL20/CCR6的表达来减轻银屑病小鼠的皮肤病变。展开更多
目的观察CC趋化因子配体20(CCL20)在银屑病皮损中的表达及作用。方法采用免疫荧光观察银屑病患者及咪喹莫特诱导银屑病样小鼠皮损中CCL20的表达。采用胶带剥脱诱导小鼠银屑病模型,用银屑病皮损面积和疾病严重程度(psoriasis area and se...目的观察CC趋化因子配体20(CCL20)在银屑病皮损中的表达及作用。方法采用免疫荧光观察银屑病患者及咪喹莫特诱导银屑病样小鼠皮损中CCL20的表达。采用胶带剥脱诱导小鼠银屑病模型,用银屑病皮损面积和疾病严重程度(psoriasis area and severity index,PASI)评分标准,观察CCL20蛋白注射后银屑病样小鼠皮损的变化;显微镜下观察皮损组织形态学变化,测量表皮层垂直厚度。采用咪喹莫特诱导小鼠银屑病模型,用PASI评分标准,观察CCL20单克隆抗体注射对银屑病样小鼠皮损的影响,显微镜下观察皮损组织形态学变化,测量表皮层垂直厚度;免疫组化观察表皮增殖的变化;real-time PCR检测小鼠皮肤组织样本中CCL20的表达。结果银屑病患者及咪喹莫特诱导银屑病样小鼠皮损中CCL20的表达增加;CCL20蛋白复合胶带剥脱组(CCL20组)小鼠银屑病样皮损程度较重,红斑、鳞屑、浸润以及表皮增厚程度高于单纯胶带剥脱模型组;CCL20单克隆抗体组(anti-CCL20组)小鼠银屑病样皮损程度较轻,红斑、鳞屑、浸润、表皮增厚以及表皮细胞增殖程度轻于咪喹莫特模型组,皮肤组织CCL20的表达明显低于模型组。结论 CCL20在银屑病皮损中呈高表达,CCL20蛋白可加重胶带剥脱诱导小鼠银屑病样皮损,CCL20单克隆抗体注射对IMQ诱导的小鼠银屑病样皮损有一定的治疗作用。展开更多
目的研究肝活检组织趋化因子CC亚家族配体20(CCL20)在慢性乙型肝炎肝组织中的表达及其意义。方法以内参照竞争性逆转录聚合酶链反应对处于乙性肝炎病毒(Hepatitis B virus,HBV)不同感染状态的肝细胞以及人肝脏活检组织CCL20mRNA的表达...目的研究肝活检组织趋化因子CC亚家族配体20(CCL20)在慢性乙型肝炎肝组织中的表达及其意义。方法以内参照竞争性逆转录聚合酶链反应对处于乙性肝炎病毒(Hepatitis B virus,HBV)不同感染状态的肝细胞以及人肝脏活检组织CCL20mRNA的表达水平进行定量分析。结果在细胞水平和肝脏组织学两个层面上,HBV不同感染状态可影响CCL20的表达水平,CCL20表达量在不同感染模式下呈现未感染>持续性感染的关系(P<0.05)。结论趋化因子CCL20在乙型肝炎病毒持续性感染中表达下调。展开更多
目的:观察凉血解毒汤对人表皮角质形成细胞(Ha Ca T细胞)CC趋化因子配体20(CCL20)表达及分泌的影响,并探讨其作用机制。方法:用IL-17(100 ng·m L-1)刺激Ha Ca T细胞,并加入不同浓度凉血解毒汤(8、2、0.5μg·m L-1),干预体外培...目的:观察凉血解毒汤对人表皮角质形成细胞(Ha Ca T细胞)CC趋化因子配体20(CCL20)表达及分泌的影响,并探讨其作用机制。方法:用IL-17(100 ng·m L-1)刺激Ha Ca T细胞,并加入不同浓度凉血解毒汤(8、2、0.5μg·m L-1),干预体外培养Ha Ca T细胞模型。采用MTT法检测凉血解毒汤剂对Ha Ca T细胞活性的影响;ELISA检测细胞上清CCL20蛋白的含量,Western blot检测细胞内CCL20相关蛋白(p-IκBα、p-P65)的变化,Realtime PCR检测细胞样本中CCL20相关基因(Piasy、Trim32 m RNA)转录水平的变化情况。结果:IL-17能够诱导Ha Ca T细胞CCL20的表达及分泌。加入凉血解毒汤水煎剂粉末后,CCL20在分泌、蛋白、m RNA表达水平均明显下降(P<0.05),NF-κB通路相关蛋白p-P65、p-IκBα磷酸化水平显著下降(P<0.01),但对CCL20相关调节分子Piasy、Trim32 m RNA的表达无显著影响(P>0.05)。结论:凉血解毒汤通过调节NF-κB通路磷酸化抑制Ha Ca T细胞分泌及表达CCL20可能是其发挥治疗银屑病作用机制之一。展开更多
文摘AIM: To identify the mechanisms of chemokine ligand 20(CCL20)-induced hepatocellular carcinoma(HCC) metastasis and evaluate it as a prognostic marker. METHODS: Expression of CCL20 was evaluated by immunohistochemistry in HCC tissues from 62 patients who underwent curative resection. The relationship between CCL20 expression and clinicopathologic features was analyzed. Univariate and multivariate analyses were performed to evaluate its predictive value for recurrence and survival of HCC patients. The expression levels ofepithelial-mesenchymal transition(EMT)-and signaling pathway-related proteins were evaluated by Western blotting and immunocytochemistry. The effects of CCL20 on HCC cell proliferation and migration were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenoltetrazolium bromide(MTT) and Transwell assays. RESULTS: CCL20 immunoreactivity was detected in all 62 patient specimens. CCL20 expression was associated with preoperative alpha-fetoprotein level(P = 0.043), tumor size(P = 0.000), tumor number(P = 0.008), vascular invasion(P = 0.014), and tumor differentiation(P = 0.007). Patients with high CCL20 expression had poorer recurrence-free and overall survivals compared to those with low CCL20 expression(both P < 0.001). CCL20 induced EMT-like changes in HCC cells and increased their proliferation and migration ability(P < 0.05). Western blotting and immunofluorescence staining showed that CCL20 induced an EMT-like phenotype in HCC cells, and increased expression of phosphorylated AKT, β-catenin and vimentin, and decreased E-cadherin expression(P < 0.05). The correlation analysis revealed that high CCL20 expression in HCC tissue specimens was negatively correlated with E-cadherin expression(13.33%, 4/30), and positively correlated with vimentin(90.0%, 27/30), β-catenin(96.67%, 29/30) and p-AKT(76.67%, 23/30) expression.CONCLUSION: CCL20 expression is associated with HCC recurrence and patient survival and promotes HCC cell proliferation and migration by inducing EMT-like changes via PI3K/AKT and Wnt/β-catenin pathways.
文摘Summary: In order to explore the possible role of CC chemokine ligand 20 (CCL20) and its receptor CC chemokine receptor 6 (CCR6) in the pathogenesis of psoriasis, the expression levels of mRNA of them in psoriatic lesions were investigated. The skin biopsies were collected from skin lesions in 35 cases of psoriasis vulgaris and 18 normal controls. RT-PCR was used to semi-quantitatively analyze the mRNA expression of CCL20 and CCR6 in the psoriatic lesions and the normal skin tissues. The results showed that the mRNA of CCL20 and CCR6 was present in every specimen. The expression levels of CCL20 mRNA in skin lesions were 1.1397±0.0521, which were greatly higher than those in normal controls (0.8681±0.0308) (P<0.001). The expression levels of CCR6 mRNA in skin lesions were 1.1103±0.0538, significantly higher than in the controls (0.9131±0.0433, P<0.001). These findings indicate that up-regulated expression of CCL20 and CCR6 mRNA might be related to the pathogenesis of psoriasis.
文摘Chemokines belong to a superfamily of small, cytokinelike proteins, which induce multiple physiological functions, particularly cytoskeletal rearrangement and compartment-specific migration through their interaction with G-protein-coupled receptors. Chemokines and their receptors have been widely acknowledged as essential and selective mediators in leukocyte migration in inflammatory response. It is now established that the chemokine/chemokine receptor system is also used by cancer cells to direct lymphatic and haematogenous spreading and additionally has an impact on the site of metastatic growth of different tumours. In recent years an increasing number of studies have drawn attention to CC-chemokine cysteine motif chemokine ligand 20(CCL20) and its physiological sole receptor CCR6 to play a role in the onset, development and metastatic spread of various gastrointestinal cancer entities. Among various cancer types CCR6 was also demonstrated to be significantly overexpressed in colorectal cancer(CRC) and stimulation by its physiological ligand CCL20 has been reported to promote CRC cell proliferation and migration in vitro. Further, the CCL20/CCR6 system apparently plays a role in the organ-selective liver metastasis of CRC. Here we review the literature on expression patterns of CCL20 and CCR6 and their physiological interactions as well as the currently presumed role of CCL20 and CCR6 in the formation of CRC and the development of liver metastasis, providing a potential basis for novel treatment strategies.
文摘目的探讨血清CC趋化因子配体20(CCL20)及白介素-17(IL-17)水平与子痫前期的相关性及其对子痫前期的诊断效能。方法选择2021年1月至2022年12月陕西省人民医院产科收治的150例子痫前期孕妇为子痫前期组,另选取同期90例健康妊娠妇女为对照组。采用酶联免疫吸附法(ELISA)检测血清CCL20及IL-17的表达水平,采用Pearson相关法分析血清CCL20及IL-17与子痫前期患者临床参数的相关性;采用受试者工作特征曲线(ROC)分析血清CCL20及IL-17对子痫前期的诊断价值。结果子痫前期组孕妇血清CCL20及IL-17水平均显著高于对照组(P<0.001)。子痫前期组孕妇血清CCL20及IL-17的表达均与收缩压(分别为r=0.463、r=0.545)、舒张压(分别为r=0.475、r=0.467)及尿蛋白(分别为r=0.302、r=0.342)呈显著正相关(P<0.001),而与终止妊娠孕周(分别为r=-0.281、r=-0.188)、新生儿出生体重(分别为r=-0.299、r=-0.200)及1 min Apgar评分(分别为r=-0.215、r=-0.194)呈显著负相关(P<0.05)。子痫前期组孕妇血清CCL20与IL-17水平呈显著正相关(r=0.615,P<0.001)。血清CCL20及IL-17诊断子痫前期的临界值分别为50.025 pg/ml及48.825 pg/ml,血清CCL20+IL-17联合诊断子痫前期的曲线下面积最大,灵敏度及特异度分别为87.3%及94.4%。结论子痫前期孕妇血清CCL20及IL-17的水平显著高于健康孕妇,且CCL20及IL-17水平与患者的血压、尿蛋白、妊娠结局及新生儿情况均存在显著相关性,两指标联合应用对子痫前期有一定的诊断价值。
文摘目的:观察凉血解毒汤对银屑病小鼠皮肤组织中CC趋化因子配体20(CCL20)/CC趋化因子受体6(CCR6)表达的干预作用。方法:24只BALB/c雄性小鼠随机分为空白对照组、银屑病模型组、凉血解毒汤中药治疗组和趋化因子CCL20单克隆抗体(阳性药)治疗组。用咪喹莫特诱导小鼠银屑病模型,采用银屑病皮损面积和疾病严重程度(psoriasis area and severity index,PASI)评分标准观察银屑病样小鼠皮损的变化情况。光镜下观察皮损组织形态学变化,测量表皮层厚度。采用real-time PCR检小鼠皮肤组织样本中CCL20和CCR6表达的变化。结果:银屑病模型组小鼠皮肤出现大量鳞屑和红斑,表皮增厚;与银屑病模型组小鼠比较,凉血解毒汤组小鼠银屑病样皮损程度较轻,红斑、鳞屑以及表皮增厚程度轻于模型组,PASI分数降低,皮肤组织CCL20以及CCR6的表达明显低于模型组。趋化因子CCL20单克隆抗体治疗组小鼠银屑病皮损程度较轻,红斑、鳞屑以及表皮增厚程度轻于模型组,PASI分数降低,皮肤组织CCL20以及CCR6的表达明显低于模型组。结论:凉血解毒汤可能通过下调CCL20/CCR6的表达来减轻银屑病小鼠的皮肤病变。
文摘目的观察CC趋化因子配体20(CCL20)在银屑病皮损中的表达及作用。方法采用免疫荧光观察银屑病患者及咪喹莫特诱导银屑病样小鼠皮损中CCL20的表达。采用胶带剥脱诱导小鼠银屑病模型,用银屑病皮损面积和疾病严重程度(psoriasis area and severity index,PASI)评分标准,观察CCL20蛋白注射后银屑病样小鼠皮损的变化;显微镜下观察皮损组织形态学变化,测量表皮层垂直厚度。采用咪喹莫特诱导小鼠银屑病模型,用PASI评分标准,观察CCL20单克隆抗体注射对银屑病样小鼠皮损的影响,显微镜下观察皮损组织形态学变化,测量表皮层垂直厚度;免疫组化观察表皮增殖的变化;real-time PCR检测小鼠皮肤组织样本中CCL20的表达。结果银屑病患者及咪喹莫特诱导银屑病样小鼠皮损中CCL20的表达增加;CCL20蛋白复合胶带剥脱组(CCL20组)小鼠银屑病样皮损程度较重,红斑、鳞屑、浸润以及表皮增厚程度高于单纯胶带剥脱模型组;CCL20单克隆抗体组(anti-CCL20组)小鼠银屑病样皮损程度较轻,红斑、鳞屑、浸润、表皮增厚以及表皮细胞增殖程度轻于咪喹莫特模型组,皮肤组织CCL20的表达明显低于模型组。结论 CCL20在银屑病皮损中呈高表达,CCL20蛋白可加重胶带剥脱诱导小鼠银屑病样皮损,CCL20单克隆抗体注射对IMQ诱导的小鼠银屑病样皮损有一定的治疗作用。
文摘目的研究肝活检组织趋化因子CC亚家族配体20(CCL20)在慢性乙型肝炎肝组织中的表达及其意义。方法以内参照竞争性逆转录聚合酶链反应对处于乙性肝炎病毒(Hepatitis B virus,HBV)不同感染状态的肝细胞以及人肝脏活检组织CCL20mRNA的表达水平进行定量分析。结果在细胞水平和肝脏组织学两个层面上,HBV不同感染状态可影响CCL20的表达水平,CCL20表达量在不同感染模式下呈现未感染>持续性感染的关系(P<0.05)。结论趋化因子CCL20在乙型肝炎病毒持续性感染中表达下调。
文摘目的:观察凉血解毒汤对人表皮角质形成细胞(Ha Ca T细胞)CC趋化因子配体20(CCL20)表达及分泌的影响,并探讨其作用机制。方法:用IL-17(100 ng·m L-1)刺激Ha Ca T细胞,并加入不同浓度凉血解毒汤(8、2、0.5μg·m L-1),干预体外培养Ha Ca T细胞模型。采用MTT法检测凉血解毒汤剂对Ha Ca T细胞活性的影响;ELISA检测细胞上清CCL20蛋白的含量,Western blot检测细胞内CCL20相关蛋白(p-IκBα、p-P65)的变化,Realtime PCR检测细胞样本中CCL20相关基因(Piasy、Trim32 m RNA)转录水平的变化情况。结果:IL-17能够诱导Ha Ca T细胞CCL20的表达及分泌。加入凉血解毒汤水煎剂粉末后,CCL20在分泌、蛋白、m RNA表达水平均明显下降(P<0.05),NF-κB通路相关蛋白p-P65、p-IκBα磷酸化水平显著下降(P<0.01),但对CCL20相关调节分子Piasy、Trim32 m RNA的表达无显著影响(P>0.05)。结论:凉血解毒汤通过调节NF-κB通路磷酸化抑制Ha Ca T细胞分泌及表达CCL20可能是其发挥治疗银屑病作用机制之一。
