Objective Proprionibacterium acnes(P.acnes)-induced inflammatory responses,proliferation and differentiation of keratinocytes contribute to the progression of acne vulgaris(AV).P.acnes was found to enhance the product...Objective Proprionibacterium acnes(P.acnes)-induced inflammatory responses,proliferation and differentiation of keratinocytes contribute to the progression of acne vulgaris(AV).P.acnes was found to enhance the production of interleukin-8(IL-8)by keratinocytes.This study aimed to investigate the role of IL-8 in P.acnes-induced proliferation and differentiation of keratinocytes and the underlying mechanism.Methods The P.acnes-stimulated HaCaT cell(a human keratinocyte cell line)model was established.Western blotting and immunofluorescence were performed to detect the expression of the IL-8 receptors C-X-C motif chemokine receptor 1(CXCR1)and C-X-C motif chemokine receptor 2(CXCR2)on HaCaT cells.Cell counting kit-8(CCK-8)assay,5-ethynyl-20-deoxyuridine(EdU)assay and Western blotting were performed to examine the effects of IL-8/CXCR2 axis on the proliferation and differentiation of HaCaT cells treated with P.acnes,the IL-8 neutralizing antibody,the CXCR2 antagonist(SB225002),or the CXCR1/CXCR2 antagonist(G31P).Western blotting,nuclear and cytoplasmic separation,CCK-8 assay,and EdU assay were employed to determine the downstream pathway of CXCR2 after P.acnes-stimulated HaCaT cells were treated with the CXCR2 antagonist,the protein kinase B(AKT)antagonist(AZD5363),or the constitutively active forkhead box O1(FOXO1)mutant.Finally,autophagy markers were measured in HaCaT cells following the transfection of the FOXO1 mutant or treatment with the autophagy inhibitor 3-methyladenine(3-MA).Results The expression levels of CXCR1 and CXCR2 were significantly increased on the membrane of HaCaT cells following P.acnes stimulation.The IL-8/CXCR2 axis predominantly promoted the proliferation and differentiation of P.acnes-induced HaCaT cells by activating AKT/FOXO1/autophagy signaling.In brief,IL-8 bound to its receptor CXCR2 on the membrane of keratinocytes to activate the AKT/FOXO1 axis.Subsequently,phosphorylated FOXO1 facilitated autophagy to promote the proliferation and differentiation of P.acnes-induced keratinocytes.Conclusion This study demonstrated the novel autocrine effect of IL-8 on the proliferation and differentiation of P.acnes-induced keratinocytes,suggesting a potential therapeutic target for AV.展开更多
目的探讨血清IL-8、IL-17对Hp阳性胃溃疡患者Hp根除率的影响。方法共174例在我院就诊的的Hp阳性胃溃疡患者,均行胃溃疡常规治疗及抗Hp三联疗法治疗。治疗前、完成3个治疗疗程后,采集患者血液检测血清IL-8、IL-17水平,并对所有患者行治疗...目的探讨血清IL-8、IL-17对Hp阳性胃溃疡患者Hp根除率的影响。方法共174例在我院就诊的的Hp阳性胃溃疡患者,均行胃溃疡常规治疗及抗Hp三联疗法治疗。治疗前、完成3个治疗疗程后,采集患者血液检测血清IL-8、IL-17水平,并对所有患者行治疗后Hp C 13呼气实验。采用Pearson相关性分析,Hp胃溃疡患者Hp根除率与患者治疗前血清IL-8、IL-17水平间的相关性。结果治疗3个疗程后,Hp阳性胃溃疡患者血清IL-8、IL-17水平水平较治疗前明显下降,Hp根除率为70.11%,治疗前观察组血清IL-8、IL-17水平明显低于对照组(P<0.05);不同年龄、不同胃溃疡病程、既往抗Hp治疗史的Hp阳性胃溃疡患者血清IL-8、IL-17水平及Hp根除率比较均有差异(P<0.05);Hp阳性胃溃疡患者治疗前血清IL-8、IL-17水平与Hp根除率呈负相关(r=-0.613、-0.497,P<0.01)。结论Hp阳性胃溃疡患者治疗后Hp根除率与治疗前血清IL-8、IL-17水平呈负相关,提示临床对Hp阳性胃溃疡患者治疗时应关注机体细胞因子IL-8、IL-17水平,并辅以改善相应的治疗措施,以提升Hp根除率。展开更多
Background:S100A8 is a member of the S100 protein family and plays a pivotal role in regulating inflammation and tumor progression.This study aimed to comprehensively assess the expression patterns and functional role...Background:S100A8 is a member of the S100 protein family and plays a pivotal role in regulating inflammation and tumor progression.This study aimed to comprehensively assess the expression patterns and functional roles of S100A8 in glioma progression.Methods:Glioma tissues were collected from 98 patients who underwent surgical treatment at Fudan University Shanghai Cancer Center.S100A8 expression in glioma tissues was analyzed using immunohistochemistry(IHC)to establish its correlation with clinicopathological features in patients.The expression and prognostic effect of S100A8 in glioma were analyzed using TCGA and CGGA public databases.Then,we investigated the role of S100A8 in glioma through a series of in vivo and in vitro experiments including Transwell,wound healing,CCK8,and intracranial tumor models.Subsequently,bioinformatics analysis,single-cell sequencing and coimmunopre-cipitation(Co-IP)were used to explore the underlying mechanism.Results:S100A8 was upregulated in gliomas compared to paracancerous tissues,and this phenotype was sig-nificantly correlated with poor prognosis.Subgroup analysis showed that S100A8 expression was higher in the high-grade glioma(HGG)group than that in the low-grade glioma(LGG)group.S100A8 overexpression in glioma cell lines promoted cell proliferation,migration and invasion,while silencing S100A8 reversed these effects.In vivo experiments showed that S100A8 knockdown can significantly reduce the tumor burden of glioma cells.Notably,S100A8 was observed to stimulate microglial M2 polarization by interacting with TLR4,which subse-quently induced NF-𝜅B signaling and IL-10 secretion within the tumor microenvironment.Conclusions:S100A8 promotes tumor progression by inducing phenotypic polarization of microglia through the TLR4/IL-10 signaling pathway in glioma.It might represent a therapeutic target for further basic research or clinical management of glioma.展开更多
基金supported by the National Natural Science Foundation of China(No.82103756).
文摘Objective Proprionibacterium acnes(P.acnes)-induced inflammatory responses,proliferation and differentiation of keratinocytes contribute to the progression of acne vulgaris(AV).P.acnes was found to enhance the production of interleukin-8(IL-8)by keratinocytes.This study aimed to investigate the role of IL-8 in P.acnes-induced proliferation and differentiation of keratinocytes and the underlying mechanism.Methods The P.acnes-stimulated HaCaT cell(a human keratinocyte cell line)model was established.Western blotting and immunofluorescence were performed to detect the expression of the IL-8 receptors C-X-C motif chemokine receptor 1(CXCR1)and C-X-C motif chemokine receptor 2(CXCR2)on HaCaT cells.Cell counting kit-8(CCK-8)assay,5-ethynyl-20-deoxyuridine(EdU)assay and Western blotting were performed to examine the effects of IL-8/CXCR2 axis on the proliferation and differentiation of HaCaT cells treated with P.acnes,the IL-8 neutralizing antibody,the CXCR2 antagonist(SB225002),or the CXCR1/CXCR2 antagonist(G31P).Western blotting,nuclear and cytoplasmic separation,CCK-8 assay,and EdU assay were employed to determine the downstream pathway of CXCR2 after P.acnes-stimulated HaCaT cells were treated with the CXCR2 antagonist,the protein kinase B(AKT)antagonist(AZD5363),or the constitutively active forkhead box O1(FOXO1)mutant.Finally,autophagy markers were measured in HaCaT cells following the transfection of the FOXO1 mutant or treatment with the autophagy inhibitor 3-methyladenine(3-MA).Results The expression levels of CXCR1 and CXCR2 were significantly increased on the membrane of HaCaT cells following P.acnes stimulation.The IL-8/CXCR2 axis predominantly promoted the proliferation and differentiation of P.acnes-induced HaCaT cells by activating AKT/FOXO1/autophagy signaling.In brief,IL-8 bound to its receptor CXCR2 on the membrane of keratinocytes to activate the AKT/FOXO1 axis.Subsequently,phosphorylated FOXO1 facilitated autophagy to promote the proliferation and differentiation of P.acnes-induced keratinocytes.Conclusion This study demonstrated the novel autocrine effect of IL-8 on the proliferation and differentiation of P.acnes-induced keratinocytes,suggesting a potential therapeutic target for AV.
文摘目的探讨血清IL-8、IL-17对Hp阳性胃溃疡患者Hp根除率的影响。方法共174例在我院就诊的的Hp阳性胃溃疡患者,均行胃溃疡常规治疗及抗Hp三联疗法治疗。治疗前、完成3个治疗疗程后,采集患者血液检测血清IL-8、IL-17水平,并对所有患者行治疗后Hp C 13呼气实验。采用Pearson相关性分析,Hp胃溃疡患者Hp根除率与患者治疗前血清IL-8、IL-17水平间的相关性。结果治疗3个疗程后,Hp阳性胃溃疡患者血清IL-8、IL-17水平水平较治疗前明显下降,Hp根除率为70.11%,治疗前观察组血清IL-8、IL-17水平明显低于对照组(P<0.05);不同年龄、不同胃溃疡病程、既往抗Hp治疗史的Hp阳性胃溃疡患者血清IL-8、IL-17水平及Hp根除率比较均有差异(P<0.05);Hp阳性胃溃疡患者治疗前血清IL-8、IL-17水平与Hp根除率呈负相关(r=-0.613、-0.497,P<0.01)。结论Hp阳性胃溃疡患者治疗后Hp根除率与治疗前血清IL-8、IL-17水平呈负相关,提示临床对Hp阳性胃溃疡患者治疗时应关注机体细胞因子IL-8、IL-17水平,并辅以改善相应的治疗措施,以提升Hp根除率。
基金supported by the National Natural Science Foundation of China(grant numbers:82103429 and 82173177).
文摘Background:S100A8 is a member of the S100 protein family and plays a pivotal role in regulating inflammation and tumor progression.This study aimed to comprehensively assess the expression patterns and functional roles of S100A8 in glioma progression.Methods:Glioma tissues were collected from 98 patients who underwent surgical treatment at Fudan University Shanghai Cancer Center.S100A8 expression in glioma tissues was analyzed using immunohistochemistry(IHC)to establish its correlation with clinicopathological features in patients.The expression and prognostic effect of S100A8 in glioma were analyzed using TCGA and CGGA public databases.Then,we investigated the role of S100A8 in glioma through a series of in vivo and in vitro experiments including Transwell,wound healing,CCK8,and intracranial tumor models.Subsequently,bioinformatics analysis,single-cell sequencing and coimmunopre-cipitation(Co-IP)were used to explore the underlying mechanism.Results:S100A8 was upregulated in gliomas compared to paracancerous tissues,and this phenotype was sig-nificantly correlated with poor prognosis.Subgroup analysis showed that S100A8 expression was higher in the high-grade glioma(HGG)group than that in the low-grade glioma(LGG)group.S100A8 overexpression in glioma cell lines promoted cell proliferation,migration and invasion,while silencing S100A8 reversed these effects.In vivo experiments showed that S100A8 knockdown can significantly reduce the tumor burden of glioma cells.Notably,S100A8 was observed to stimulate microglial M2 polarization by interacting with TLR4,which subse-quently induced NF-𝜅B signaling and IL-10 secretion within the tumor microenvironment.Conclusions:S100A8 promotes tumor progression by inducing phenotypic polarization of microglia through the TLR4/IL-10 signaling pathway in glioma.It might represent a therapeutic target for further basic research or clinical management of glioma.
基金江苏省科技支撑计划(BE2012310)Financially Supported by Special Foundation for Clinical Studies from Committee of Medical Journal of Chinese Universities(11221022)
