1.Therapeuti ceffect and potential mechanism of cholesterol sulfate on a mouse model of Hashimoto's thyroiditis
Linye HE ; Huandi QIU ; Wei HE ; Yiguo HU ; Zhihui LI
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(1):105-111
Objective To investigate the therapeutic effect of cholesterol sulfate(CS)on the Hashimoto's thyroiditis mouse model.Methods Female NOD.H-2h4 mice were fed with 0.05%NaI in different periods and treated with CS by intraperitoneal injection for two consecutive weeks.HE staining was used to visualize and score the degree of lymphocyte infiltration in the thyroid;serum levels of thyroglobulin antibody(TgAb),thyroid peroxidase antibody(TPOAb),thyroxine(T4),and thyroid stimulating hormone(TSH)were detected by ELISA.The proportions of B cells and Treg,Th17,Th1,and Th2 cells were analyzed by immunofluorescence staining flow cytometry.Results HE staining showed that the inflammatory score of thyroid tissue in mice after intraperitoneal injection of CS in the 8-week group and the 16-week group decreased significantly(P<0.05).In the 64-week group,there was no significant difference between the treatment group and the induction group(P=0.31).Serological analysis showed that after CS intervention,the levels of TgAb and TPOAb in mice induced by 0.05%NaI significantly lowered(P<0.05)in the 8-week group and the 16-week group,while thyroid function(TSH and T4 levels)of the mice changed significantly only in the 16-week group.Flow cytometry analysis showed that in the 8-week group,after CS intervention the proportions of B lymphocytes and Th1,Th2,Th17 and Treg cells in mice were significantly changed(P<0.05).Conclusion CS has significant therapeutic and remission effects on the early and middle stages of Hashimoto's thyroiditis.
2.Retinal transcriptome profile in mice following dexamethasone treatment for endotoxin-induced uveitis
Peng YU ; Yiguo QIU ; Ru LIN ; Xinyu FU ; Bingtao HAO ; Bo LEI
Journal of Southern Medical University 2018;38(8):901-909
Objective To investigate the changes in retinal transcriptome profile of mice with endotoxin-induced uveitis (EIU) following dexamethasone (DEX) treatment and explore the mechanisms underlying the therapeutic effect of DEX.Methods EIU was induced in BALB/c mice by intravitreal injection of 125 ng lipopolysaccharide (LPS),followed by topical application of DEX (0.1%) eye drops every 4 h for 24 h.The anterior chamber inflammation was examined with a slit lamp and the clinical scores were assessed.The morphological changes in the eyes were assessed at 24 h after LPS injection.The retinas were harvested for analysis of transcriptome profile using the next-generation sequencing (NGS)-based RNA sequencing (RNA-seq),and the expressions of the inflammatory cytokines and the differentially expressed genes (DEGs) were verified using real-time PCR.Results DEX alleviated the inflammatory response and reduced the mRNA expressions of IL-6,TNF-α,MCP-1 and ICAM-1 at 24 h after LPS injection.A total of 52 DEGs were identified by RNA-seq.Within these DEGs,37 genes were upregulated and 15 genes were down-regulated in LPS group as compared with DEX+LPS group.No significantly enriched Gene Ontology (GO) terms was noted.Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed 6 up-regulated and 2 down-regulated KEGG pathways.RIG-I-like receptor signaling pathway and several immune-and inflammation-related genes including Ifit1,H2-T24,Mx2 and Eif2ak2 were significantly down regulated by DEX.Verification with RT-PCR yielded results consistent with these findings.Conclusion DEX alleviates LPS-induced inflammatory response in the retina of mice,and such protective effect is probably mediated by RIG-I like receptor signal pathway and the immune-and inflammation-related genes.
3.Retinal transcriptome profile in mice following dexamethasone treatment for endotoxin-induced uveitis
Peng YU ; Yiguo QIU ; Ru LIN ; Xinyu FU ; Bingtao HAO ; Bo LEI
Journal of Southern Medical University 2018;38(8):901-909
Objective To investigate the changes in retinal transcriptome profile of mice with endotoxin-induced uveitis (EIU) following dexamethasone (DEX) treatment and explore the mechanisms underlying the therapeutic effect of DEX.Methods EIU was induced in BALB/c mice by intravitreal injection of 125 ng lipopolysaccharide (LPS),followed by topical application of DEX (0.1%) eye drops every 4 h for 24 h.The anterior chamber inflammation was examined with a slit lamp and the clinical scores were assessed.The morphological changes in the eyes were assessed at 24 h after LPS injection.The retinas were harvested for analysis of transcriptome profile using the next-generation sequencing (NGS)-based RNA sequencing (RNA-seq),and the expressions of the inflammatory cytokines and the differentially expressed genes (DEGs) were verified using real-time PCR.Results DEX alleviated the inflammatory response and reduced the mRNA expressions of IL-6,TNF-α,MCP-1 and ICAM-1 at 24 h after LPS injection.A total of 52 DEGs were identified by RNA-seq.Within these DEGs,37 genes were upregulated and 15 genes were down-regulated in LPS group as compared with DEX+LPS group.No significantly enriched Gene Ontology (GO) terms was noted.Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed 6 up-regulated and 2 down-regulated KEGG pathways.RIG-I-like receptor signaling pathway and several immune-and inflammation-related genes including Ifit1,H2-T24,Mx2 and Eif2ak2 were significantly down regulated by DEX.Verification with RT-PCR yielded results consistent with these findings.Conclusion DEX alleviates LPS-induced inflammatory response in the retina of mice,and such protective effect is probably mediated by RIG-I like receptor signal pathway and the immune-and inflammation-related genes.