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
Psoriasiform rash is a notable immune-related cutaneous adverse event(ircAE)accounting for approximately 5%of all ircAEs1,2.Patients with cancer and pre-existing psoriasis face elevated risk of disease recurrence or e...Psoriasiform rash is a notable immune-related cutaneous adverse event(ircAE)accounting for approximately 5%of all ircAEs1,2.Patients with cancer and pre-existing psoriasis face elevated risk of disease recurrence or exacerbation after receiving immune checkpoint inhibitors(ICIs).A European multicenter study has reported a reactivation rate of 28.7%in this population3.ICIs also trigger de novo psoriatic lesions,which mirror conventional lesion subtypes(plaque,guttate,erythrodermic,or pustular).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supported by grants from the National Natural Science Foundation of China(Nos.82373372 and U22A20330)Key Project of Research and Development Plan in Heilongjiang Province(Nos.2022ZX06C01 and JD2023SJ40)+1 种基金National Cancer Center Climbing Fund(No.NCC201908A03)Beijing Xisike Clinical Oncology Research Foundation(No.Y-HR2020MS-0900).
文摘Psoriasiform rash is a notable immune-related cutaneous adverse event(ircAE)accounting for approximately 5%of all ircAEs1,2.Patients with cancer and pre-existing psoriasis face elevated risk of disease recurrence or exacerbation after receiving immune checkpoint inhibitors(ICIs).A European multicenter study has reported a reactivation rate of 28.7%in this population3.ICIs also trigger de novo psoriatic lesions,which mirror conventional lesion subtypes(plaque,guttate,erythrodermic,or pustular).
