BACKGROUND Oxidized low-density lipoprotein(ox-LDL),which is abnormally increased in the serum of colorectal cancer(CRC)patients consuming a high-fat diet(HFD),may be one of the risk factors for the development of CRC...BACKGROUND Oxidized low-density lipoprotein(ox-LDL),which is abnormally increased in the serum of colorectal cancer(CRC)patients consuming a high-fat diet(HFD),may be one of the risk factors for the development of CRC.Ox-LDL exerts a regulatory effect on macrophages and may influence CRC through the tumor microenvironment.The role of ox-LDL in CRC remains unclear.AIM To investigate the role of ox-LDL through macrophages in HFD associated CRC.METHODS The expression of ox-LDL and CD206 was detected in colorectal tissues of CRC patients with hyperlipidemia and HFD-fed mice by immunofluorescence.We stimulated the macrophages with 20μg/mL ox-LDL and assessed the expression levels of CD206 and the cytokines by cell fluorescence and quantitative polymerase chain reaction.We further knocked down LOX-1,the surface receptor of ox-LDL,to confirm the function of ox-LDL in macrophages.Then,LoVo cells were co-cultured with the stimulated macrophages to analyze the CD44 and CD133 expression by western blot.RESULTS The expression of ox-LDL and the CD206 was significantly increased in the stroma of colorectal tissues of CRC patients with hyperlipidemia,and also upregulated in the HFD-fed mice.Moreover,an increased level of CD206 and decreased level of inducible nitric oxide synthase were observed in macrophages after ox-LDL continuous stimulation.Such effects were inhibited when the surface receptor LOX-1 was knocked down in macrophages.Ox-LDL could induce CD206+macrophages,which resulted in high expression of CD44 and CD133 in co-cultured LoVo cells.CONCLUSION Ox-LDL stimulates CD206+macrophages to upregulate CD44 and CD133 expression in HFD related CRC.展开更多
目的弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)预后因素尚不明确.本研究探讨TLR4、CD163和CD206在DLBCL组织表达及临床意义,并寻找新的DLBCL预后指标.方法回顾性分析2011-06-01-2017-06-30中南大学湘雅医学院附属海口医...目的弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)预后因素尚不明确.本研究探讨TLR4、CD163和CD206在DLBCL组织表达及临床意义,并寻找新的DLBCL预后指标.方法回顾性分析2011-06-01-2017-06-30中南大学湘雅医学院附属海口医院确诊的84例DLBCL患者,收集患者临床资料、治疗及预后信息,采用免疫组织化学法检测DLBCL组织中TLR4、CD163和CD206分子表达,分析其表达程度与临床病理特征及预后关系,组间比较采用χ^2检验,应用Kaplan-Meier法绘制生存曲线,Log-rank法进行曲线间单因素分析,多因素分析采用Cox回归模型.结果 TLR4蛋白表达阳性与LDH水平升高有关联,其中LDH水平升高者占TLR4蛋白表达阳性患者的58.1%(25/43),差异有统计学意义,χ^2=4.858,P=0.031.TLR4、CD163和CD206蛋白表达在患者年龄、性别、Ann Arbor分期、美国东部肿瘤协作组评分、国际预后指数评分、B症状、Hans法分型之间差异均无统计学意义,均P>0.05.Spearman秩次相关分析结果显示,在DLBCL组织中TLR4与CD163(r=0.167,P=0.190)和CD206表达(r=0.191,P=0.087)无关联.单因素分析显示,年龄(χ^2=5.192,P=0.023)、TLR4(χ^2=5.772,P=0.016)和CD206表达水平(χ^2=4.575,P=0.032)与中位无进展生存期有关联,CD206表达水平(χ^2=5.060,P=0.024)与中位总生存期有关联.多因素分析显示,TLR4(HR=1.755,P=0.019)和CD206(HR=1.638,P=0.036)是影响无进展生存期独立预后危险性因素;CD206(HR=1.668,P=0.029)是影响总生存期独立预后危险性因素.结论TLR4和CD206蛋白表达对判断DLBCL患者预后有一定临床价值,有望成为评估DLBCL预后的新指标.展开更多
文摘BACKGROUND Oxidized low-density lipoprotein(ox-LDL),which is abnormally increased in the serum of colorectal cancer(CRC)patients consuming a high-fat diet(HFD),may be one of the risk factors for the development of CRC.Ox-LDL exerts a regulatory effect on macrophages and may influence CRC through the tumor microenvironment.The role of ox-LDL in CRC remains unclear.AIM To investigate the role of ox-LDL through macrophages in HFD associated CRC.METHODS The expression of ox-LDL and CD206 was detected in colorectal tissues of CRC patients with hyperlipidemia and HFD-fed mice by immunofluorescence.We stimulated the macrophages with 20μg/mL ox-LDL and assessed the expression levels of CD206 and the cytokines by cell fluorescence and quantitative polymerase chain reaction.We further knocked down LOX-1,the surface receptor of ox-LDL,to confirm the function of ox-LDL in macrophages.Then,LoVo cells were co-cultured with the stimulated macrophages to analyze the CD44 and CD133 expression by western blot.RESULTS The expression of ox-LDL and the CD206 was significantly increased in the stroma of colorectal tissues of CRC patients with hyperlipidemia,and also upregulated in the HFD-fed mice.Moreover,an increased level of CD206 and decreased level of inducible nitric oxide synthase were observed in macrophages after ox-LDL continuous stimulation.Such effects were inhibited when the surface receptor LOX-1 was knocked down in macrophages.Ox-LDL could induce CD206+macrophages,which resulted in high expression of CD44 and CD133 in co-cultured LoVo cells.CONCLUSION Ox-LDL stimulates CD206+macrophages to upregulate CD44 and CD133 expression in HFD related CRC.
