IL-33 and its receptor ST2 play crucial roles in tissue repair and homeostasis.However,their involvement in optic neuropathy due to trauma and glaucoma remains unclear.Here,we report that IL-33 and ST2 were highly exp...IL-33 and its receptor ST2 play crucial roles in tissue repair and homeostasis.However,their involvement in optic neuropathy due to trauma and glaucoma remains unclear.Here,we report that IL-33 and ST2 were highly expressed in the mouse optic nerve and retina.Deletion of IL-33 or ST2 exacerbated retinal ganglion cell(RGC)loss,retinal thinning,and nerve fiber degeneration following optic nerve(ON)injury.This heightened retinal neurodegeneration correlated with increased neurotoxic astrocytes in Il33-/-mice.In vitro,rIL-33 mitigated the neurotoxic astrocyte phenotype and reduced the expression of pro-inflammatory factors,thereby alleviating the RGC death induced by neurotoxic astrocyte-conditioned medium in retinal explants.Exogenous IL-33 treatment improved RGC survival in Il33-/-and WT mice after ON injury,but not in ST2-/-mice.Our findings highlight the role of the IL-33/ST2 axis in modulating reactive astrocyte function and providing neuroprotection for RGCs following ON injury.展开更多
Objective:Suppression of tumorigenicity 2(ST2),the receptor for interleukin(IL)-33,has a critical role in tumor growth,angiogenesis,metastasis,and immune modulation.The IL-33/ST2 pathway is known to influence the pola...Objective:Suppression of tumorigenicity 2(ST2),the receptor for interleukin(IL)-33,has a critical role in tumor growth,angiogenesis,metastasis,and immune modulation.The IL-33/ST2 pathway is known to influence the polarization and function of macrophages,which is integral to modulating the tumor microenvironment.However,the precise role of IL-33/ST2 in tumors,particularly non-small cell lung cancer(NSCLC),has not been established.Methods:ST2 expression in NSCLC was analysed using a murine model and patient specimens.The effect of the IL-33/ST2 axis on macrophage polarization in NSCLC was determined.Results:Elevated ST2 expression was correlated with aggressive tumor growth.Specifically,ST2 expression on macrophages was associated with lung cancer progression and the absence of ST2 on macrophages was associated with diminished tumor growth.IL-33 promoted polarization of alternatively activated macrophages in an ST2-dependent manner that was mediated via the PI3K/Akt signalling pathway.Moreover,IL-33 inhibited T-cell function by inducing the secretion of transforming growth factorβfrom alternatively activated macrophages.Conclusions:Macrophages expressing ST2 can serve as promising therapeutic targets for NSCLC immunotherapy,highlighting the IL-33/ST2 axis as a potential target for future antitumor strategies.展开更多
OBJECTIVE:To identify the main active ingredients of Improved Yupingfeng Powder prescription(IYPFP,玉屏风散加味)and investigate its anti-inflammatory effects and underlying mechanisms in ovalbumins(OVA)-induced allerg...OBJECTIVE:To identify the main active ingredients of Improved Yupingfeng Powder prescription(IYPFP,玉屏风散加味)and investigate its anti-inflammatory effects and underlying mechanisms in ovalbumins(OVA)-induced allergic rhinitis(AR)in mice.METHODS:Bagg Albino/substrain mice were sensitized with OVA emulsified in aluminum hydroxide adjuvant,followed by intranasal challenge to establish AR models.Treatment groups received IYPFP(1.5 or 4.5 g/kg)via daily gavage for 14 d.The nasal mucosa tissues were collected for pathological observation.The expression of OVA-specific immunoglobulin E(Ig E),histamine,and interleukin-33(IL-33)was detected by enzyme-linked immunosorbent assay.IL-5,IL-13,IL-33,suppression of tumorigenicity 2(ST2),tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)in the nasal mucosa and lung were detected by quantitative polymerase chain reaction and Western blot.High performance liquid chromatography and ultra-high performance liquid chromatography quadrupole exactive orbitrap mass spectrometry were used to detect the chemical fingerprints of IYPFP,and the chemical compositions of plasma from rats treated with IYPFP at 0.5,1,1.5,2,3,4 and 6 h,respectively.Virtual screening of bioactive compounds was conducted through molecular docking targeting IL-33/ST2 pathway proteins.RESULTS:Eight chemical compounds of IYPFP were accurately identified,they are prim-O-glucosylcimifugin(peak 2),calycosin-7-O-β-D-glucoside(peak 4),cimifugin(peak 5),5-O-methylvisammioside(peak 6),sec-Oglucosylhamaudol(peak 12),calycosin(peak 15),formononetin(peak 19),and magnolin(peak 21).Compared with the OVA model group,IYPFP alleviated the nasal symptoms,improved nasal mucosal injury and downregulated the levels of OVA-specific Ig E,histamine and IL-33.Additionally,IYPFP reduced the levels of IL-5,IL-13,TNF-α,IL-33,and ST2 in the lungs,but upregulated IFN-γ.Molecular docking confirmed that eight representative compounds of IYPFP had good binding properties with IL-5,IL-13,IFN-γ,histamine,IL-33 and ST2,and were able to inhibit the activation of the IL33/ST2 inflammatory pathway.CONCLUSION:This study demonstrates that IYPFP ameliorates AR by modulating IL-33/ST2 pathway which provides a theoretical basis for the clinical treatment of patients with AR.展开更多
基金supported by the National Natural Science Foundation of China(31670876 and 82171761).
文摘IL-33 and its receptor ST2 play crucial roles in tissue repair and homeostasis.However,their involvement in optic neuropathy due to trauma and glaucoma remains unclear.Here,we report that IL-33 and ST2 were highly expressed in the mouse optic nerve and retina.Deletion of IL-33 or ST2 exacerbated retinal ganglion cell(RGC)loss,retinal thinning,and nerve fiber degeneration following optic nerve(ON)injury.This heightened retinal neurodegeneration correlated with increased neurotoxic astrocytes in Il33-/-mice.In vitro,rIL-33 mitigated the neurotoxic astrocyte phenotype and reduced the expression of pro-inflammatory factors,thereby alleviating the RGC death induced by neurotoxic astrocyte-conditioned medium in retinal explants.Exogenous IL-33 treatment improved RGC survival in Il33-/-and WT mice after ON injury,but not in ST2-/-mice.Our findings highlight the role of the IL-33/ST2 axis in modulating reactive astrocyte function and providing neuroprotection for RGCs following ON injury.
基金supported by the National Key R&D Program of China(2023YFC2413100)the National Natural Science Foundation of China(No.81501423)the Fundamental Research Funds for the Central Universities。
文摘Objective:Suppression of tumorigenicity 2(ST2),the receptor for interleukin(IL)-33,has a critical role in tumor growth,angiogenesis,metastasis,and immune modulation.The IL-33/ST2 pathway is known to influence the polarization and function of macrophages,which is integral to modulating the tumor microenvironment.However,the precise role of IL-33/ST2 in tumors,particularly non-small cell lung cancer(NSCLC),has not been established.Methods:ST2 expression in NSCLC was analysed using a murine model and patient specimens.The effect of the IL-33/ST2 axis on macrophage polarization in NSCLC was determined.Results:Elevated ST2 expression was correlated with aggressive tumor growth.Specifically,ST2 expression on macrophages was associated with lung cancer progression and the absence of ST2 on macrophages was associated with diminished tumor growth.IL-33 promoted polarization of alternatively activated macrophages in an ST2-dependent manner that was mediated via the PI3K/Akt signalling pathway.Moreover,IL-33 inhibited T-cell function by inducing the secretion of transforming growth factorβfrom alternatively activated macrophages.Conclusions:Macrophages expressing ST2 can serve as promising therapeutic targets for NSCLC immunotherapy,highlighting the IL-33/ST2 axis as a potential target for future antitumor strategies.
基金National Natural Science Foundation of China:Exploring the Mechanism of Improved Yupingfeng Powder in Treating Allergic Rhinitis Based on the Nucleotide-Binding Oligomerization Domain,Leucine-rich Repeat and Pyrin Domain-containing Protein 3/Interleukin-33-Mediated Activation Pathway of Pulmonary Group 2 Innate Lymphoid Cells in Airway Epithelial Cells(No.82374526)Science and Technology Project of Guangzhou:Mechanism of Shikonin in Treating Acute Lung Injury Through Regulating M1 Macrophage Polarization via Adenosine 5'-monophosphate-Activated Protein Kinase/Dynamin-Related Protein 1-mediated Mitochondrial Dynamics(No.2024A04J4334)+2 种基金Exemplary Study on Process Optimization and Quality Standard Enhancement of Hospital Preparations Such as Gangmei Qingyan Mixture(No.2023A03J0299)Anti-Allergic Mechanism of Improved Yupingfeng Powder in Alleviating Nasal Mucosal Inflammation in Allergic Rhinitis via Interleukin-33/Suppression of Tumorigenicity 2-Regulated Group 2 Innate Lymphoid Cells Suppression(No.202201020457)Elite Talent Program of the First Affiliated Hospital of Guangzhou University of Chinese Medicine by 2023 Years and Guangdong Province Lingnan Characteristic Hospital Preparation Transformation Engineering Technology Research Center(No.2023A170)。
文摘OBJECTIVE:To identify the main active ingredients of Improved Yupingfeng Powder prescription(IYPFP,玉屏风散加味)and investigate its anti-inflammatory effects and underlying mechanisms in ovalbumins(OVA)-induced allergic rhinitis(AR)in mice.METHODS:Bagg Albino/substrain mice were sensitized with OVA emulsified in aluminum hydroxide adjuvant,followed by intranasal challenge to establish AR models.Treatment groups received IYPFP(1.5 or 4.5 g/kg)via daily gavage for 14 d.The nasal mucosa tissues were collected for pathological observation.The expression of OVA-specific immunoglobulin E(Ig E),histamine,and interleukin-33(IL-33)was detected by enzyme-linked immunosorbent assay.IL-5,IL-13,IL-33,suppression of tumorigenicity 2(ST2),tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)in the nasal mucosa and lung were detected by quantitative polymerase chain reaction and Western blot.High performance liquid chromatography and ultra-high performance liquid chromatography quadrupole exactive orbitrap mass spectrometry were used to detect the chemical fingerprints of IYPFP,and the chemical compositions of plasma from rats treated with IYPFP at 0.5,1,1.5,2,3,4 and 6 h,respectively.Virtual screening of bioactive compounds was conducted through molecular docking targeting IL-33/ST2 pathway proteins.RESULTS:Eight chemical compounds of IYPFP were accurately identified,they are prim-O-glucosylcimifugin(peak 2),calycosin-7-O-β-D-glucoside(peak 4),cimifugin(peak 5),5-O-methylvisammioside(peak 6),sec-Oglucosylhamaudol(peak 12),calycosin(peak 15),formononetin(peak 19),and magnolin(peak 21).Compared with the OVA model group,IYPFP alleviated the nasal symptoms,improved nasal mucosal injury and downregulated the levels of OVA-specific Ig E,histamine and IL-33.Additionally,IYPFP reduced the levels of IL-5,IL-13,TNF-α,IL-33,and ST2 in the lungs,but upregulated IFN-γ.Molecular docking confirmed that eight representative compounds of IYPFP had good binding properties with IL-5,IL-13,IFN-γ,histamine,IL-33 and ST2,and were able to inhibit the activation of the IL33/ST2 inflammatory pathway.CONCLUSION:This study demonstrates that IYPFP ameliorates AR by modulating IL-33/ST2 pathway which provides a theoretical basis for the clinical treatment of patients with AR.
