AIM:To investigate whether interleukin-17A(IL-17A)gets involved in the mechanisms of inflammation-related retinal pigment epithelium(RPE)cells injury and its significance in age-related macular degeneration(AMD).MRTHO...AIM:To investigate whether interleukin-17A(IL-17A)gets involved in the mechanisms of inflammation-related retinal pigment epithelium(RPE)cells injury and its significance in age-related macular degeneration(AMD).MRTHODS:A sodium iodate(NaIO3)mouse model as well as IL-17A-/-mice were established.The effects of inflammatory cytokines in RPE cells and retinal microglia before and after NaIO3 modeling in vivo and in vitro,were investigated using immunofluorescence,immunoprotein blotting,and quantitative real-time fluorescence polymerase chain reaction(qRT-PCR),respectively.Interventions using recombinant IL-17A protein(rIL-17A)or IL-17A neutralizing antibody(IL-17A NAb)were used to observe the subsequent differences in fundus,fundus photography and optical coherence tomography(OCT),cell viability,and expression of oxidative stress-related markers before and after modeling,and to screen for key signaling pathways.RESULTS:In the scenario of NaIO3 stimulation,RPE cells obviously tended to degenerate.Simultaneously proliferation and activation of retinal microglia was confirmed in NaIO3-stimulated mice,whereas such effects induced by NaIO3 were significantly ameliorated with IL-17A NAb intervention or in IL-17A-/-mice.In addition,IL-17A promoted the proliferation and activation of microglia as well as oxidative damage and the secretion of inflammatory cytokines alongside NaIO3-induced damage in RPE cells in vivo and ex vivo.Meanwhile,the extracellular signalregulated kinase(ERK)signaling pathway was shown to be participated in the regulation of NaIO3-induced RPE cells injury mediated by IL-17A in vivo and ex vivo,as IL-17A induced inflammatory cytokines release in the NaIO3 model was alleviated after blocking the ERK pathway.CONCLUSION:IL-17A probably promotes the NaIO3-induced RPE cells injury through exacerbating inflammation in terms of retinal microglia activation and inflammatory cytokines release via ERK signaling pathway.Inhibition of IL-17A may be a new potential target for dry AMD treatment.展开更多
The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)inductio...The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.展开更多
目的探讨祛湿清热针刺疗法对急性湿疹患者AhR、IFN-γ、EOS、IL-17水平的影响。方法选取2021年11月—2023年7月期间于马鞍山中医院收治的78例急性湿疹患者,采用随机数字表法分为对照组和治疗组,每组各39例。对照组给予常规治疗,治疗组...目的探讨祛湿清热针刺疗法对急性湿疹患者AhR、IFN-γ、EOS、IL-17水平的影响。方法选取2021年11月—2023年7月期间于马鞍山中医院收治的78例急性湿疹患者,采用随机数字表法分为对照组和治疗组,每组各39例。对照组给予常规治疗,治疗组给予祛湿清热针刺疗法治疗。治疗2周后,观察比较两组患者临床疗效、不良反应情况,治疗前后中医证候评分、湿疹面积及严重度指数(Eczema area and severity index,EASI)评分、视觉模拟评分法(Visual pain scale,VAS)评分、实验室检查指标[嗜酸性粒细胞(Eosinophil,EOS)、白细胞介素-17(Interleukin-17,IL-17)、干扰素-γ(Interferon,IFN-γ)、芳香烃受体(Aromatic hydrocarbon receptor,AhR)]、皮肤生理功能指标。结果治疗后治疗组临床总有效率97.44%(38/39)明显高于对照组82.05%(32/39),差异有统计学意义(P<0.05)。治疗后两组患者发病急、病程短、渗出明显、皮损潮红、伴红疹、灼热瘙痒、自觉发热、口渴欲饮、心烦评分均较治疗前降低,差异有统计学意义(P<0.05);且治疗组患者发病急、病程短、渗出明显、皮损潮红、伴红疹、灼热瘙痒、自觉发热、口渴欲饮、心烦评分均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者EASI、VAS评分均较治疗前降低,差异有统计学意义(P<0.05);且治疗组EASI、VAS评分均较对照组明显降低,差异有统计学意义(P<0.05)。治疗后两组患者AhR、IL-17、IFN-γ、EOS水平均较治疗前降低,差异有统计学意义(P<0.05);且治疗组AhR、IL-17、IFN-γ、EOS水平均较对照组明显降低,差异有统计学意义(P<0.05)。治疗后两组患者皮肤生理功能指标较治疗前升高,差异有统计学意义(P<0.05);且治疗组皮肤生理功能指标较对照组明显升高,差异有统计学意义(P<0.05)。治疗期间,治疗组不良反应发生率7.69%(3/39)与对照组17.95%(7/39)比较,差异无统计学意义(P>0.05)。结论祛湿清热针刺疗法能够有效降低急性湿疹患者AhR、IFN-γ、EOS、IL-17水平,降低炎症反应,疗效明显。展开更多
基金Supported by the National Natural Science Foundation of China(No.82171076,No.U22A20311,No.82388101)the National Key R&D Program(No.2022YFC2502800)Shanghai Municipal Education Commission(No.2023KJ05-67).
文摘AIM:To investigate whether interleukin-17A(IL-17A)gets involved in the mechanisms of inflammation-related retinal pigment epithelium(RPE)cells injury and its significance in age-related macular degeneration(AMD).MRTHODS:A sodium iodate(NaIO3)mouse model as well as IL-17A-/-mice were established.The effects of inflammatory cytokines in RPE cells and retinal microglia before and after NaIO3 modeling in vivo and in vitro,were investigated using immunofluorescence,immunoprotein blotting,and quantitative real-time fluorescence polymerase chain reaction(qRT-PCR),respectively.Interventions using recombinant IL-17A protein(rIL-17A)or IL-17A neutralizing antibody(IL-17A NAb)were used to observe the subsequent differences in fundus,fundus photography and optical coherence tomography(OCT),cell viability,and expression of oxidative stress-related markers before and after modeling,and to screen for key signaling pathways.RESULTS:In the scenario of NaIO3 stimulation,RPE cells obviously tended to degenerate.Simultaneously proliferation and activation of retinal microglia was confirmed in NaIO3-stimulated mice,whereas such effects induced by NaIO3 were significantly ameliorated with IL-17A NAb intervention or in IL-17A-/-mice.In addition,IL-17A promoted the proliferation and activation of microglia as well as oxidative damage and the secretion of inflammatory cytokines alongside NaIO3-induced damage in RPE cells in vivo and ex vivo.Meanwhile,the extracellular signalregulated kinase(ERK)signaling pathway was shown to be participated in the regulation of NaIO3-induced RPE cells injury mediated by IL-17A in vivo and ex vivo,as IL-17A induced inflammatory cytokines release in the NaIO3 model was alleviated after blocking the ERK pathway.CONCLUSION:IL-17A probably promotes the NaIO3-induced RPE cells injury through exacerbating inflammation in terms of retinal microglia activation and inflammatory cytokines release via ERK signaling pathway.Inhibition of IL-17A may be a new potential target for dry AMD treatment.
基金National Natural Science Foundation of China(Grants Numbers 81902878 and 81971468).
文摘The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.
文摘目的探讨祛湿清热针刺疗法对急性湿疹患者AhR、IFN-γ、EOS、IL-17水平的影响。方法选取2021年11月—2023年7月期间于马鞍山中医院收治的78例急性湿疹患者,采用随机数字表法分为对照组和治疗组,每组各39例。对照组给予常规治疗,治疗组给予祛湿清热针刺疗法治疗。治疗2周后,观察比较两组患者临床疗效、不良反应情况,治疗前后中医证候评分、湿疹面积及严重度指数(Eczema area and severity index,EASI)评分、视觉模拟评分法(Visual pain scale,VAS)评分、实验室检查指标[嗜酸性粒细胞(Eosinophil,EOS)、白细胞介素-17(Interleukin-17,IL-17)、干扰素-γ(Interferon,IFN-γ)、芳香烃受体(Aromatic hydrocarbon receptor,AhR)]、皮肤生理功能指标。结果治疗后治疗组临床总有效率97.44%(38/39)明显高于对照组82.05%(32/39),差异有统计学意义(P<0.05)。治疗后两组患者发病急、病程短、渗出明显、皮损潮红、伴红疹、灼热瘙痒、自觉发热、口渴欲饮、心烦评分均较治疗前降低,差异有统计学意义(P<0.05);且治疗组患者发病急、病程短、渗出明显、皮损潮红、伴红疹、灼热瘙痒、自觉发热、口渴欲饮、心烦评分均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者EASI、VAS评分均较治疗前降低,差异有统计学意义(P<0.05);且治疗组EASI、VAS评分均较对照组明显降低,差异有统计学意义(P<0.05)。治疗后两组患者AhR、IL-17、IFN-γ、EOS水平均较治疗前降低,差异有统计学意义(P<0.05);且治疗组AhR、IL-17、IFN-γ、EOS水平均较对照组明显降低,差异有统计学意义(P<0.05)。治疗后两组患者皮肤生理功能指标较治疗前升高,差异有统计学意义(P<0.05);且治疗组皮肤生理功能指标较对照组明显升高,差异有统计学意义(P<0.05)。治疗期间,治疗组不良反应发生率7.69%(3/39)与对照组17.95%(7/39)比较,差异无统计学意义(P>0.05)。结论祛湿清热针刺疗法能够有效降低急性湿疹患者AhR、IFN-γ、EOS、IL-17水平,降低炎症反应,疗效明显。
