Objective:The main pathological feature of immunoglobulin A nephropathy(IgAN),an autoimmune kidney disease,is the deposition of IgA immune complexes,accompanied by mesangial cell proliferation and elevated urine protein.The Guben Tongluo formula(GTF)is a traditional Chinese medicine prescription,which has predominant protective effects on IgAN.However,the therapeutic mechanism of the GTF in IgAN remains elusive.The present study aimed to determine the effects of GTF in treating IgAN via regulating the TLR4/MyD88/NF-κB pathway.Methods:In the present study,lamina propria B lymphocytes were treated with different concentrations of lipopolysaccharide(LPS)(0,1,5,10 and 20 ng/mL).Flow cytometry was used to define positive CD86+CD19+cells.CCK-8 assay was used to examine cell proliferation.RNAi was used to induce TLR4 silencing.qRT-PCR and Western blotting were used to determine gene expression.Results:It was found that the LPS dose-dependently increased the content of IgA and galactose-deficient IgAl(Gd-IgA),the levels of TLR4,Cosmc,MyD88 and phosphorylated(p)-NF-κB,and the ratio of CD86+CD19+and IgA-producing B cells.However,the TLR4 knockdown reversed the role of LPS.This suggests that TLR4 mediates the effects of LPS on lamina propria B lymphocytes.Furthermore,the GTF could dose-dependently counteract the effects of LPS and TLR4 overexpression on lamina propria B lymphocytes through the TLR4/MyD88/NF-κB pathway.Conclusion:Collectively,these results demonstrate that the GTF can regulate the TLR4/MyD88/NF-κB pathway to treat IgAN model lamina propria B lymphocytes stimulated by LPS.

Qing WU;Wei MENG;Jiao-jiao SHEN;Jia-yuan BAI;Luo-bing WANG;Ting-yu LIANG;Di HUANG;Pei-cheng SHEN

Department of Nephrology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Department of Clinical Laboratory,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Department of Nursing,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai201203,China;Department of Pathology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Key Laboratory of Liver and Kidney Diseases,Shanghai 201203,China;Key Laboratory of Liver and Kidney Diseases(Shanghai University of Traditional Chinese Medicine),Ministry of Education,Shanghai 201203,China;Shanghai Key Laboratory of Traditional Chinese Clinical Medicine(20DZ2272200),Shanghai 201203,China

当代医学科学(英文)

[1]Qing WU;Wei MENG;Jiao-jiao SHEN;Jia-yuan BAI;Luo-bing WANG;Ting-yu LIANG;Di HUANG;Pei-cheng SHEN-.Guben Tongluo Formula Protects LPS-induced Damage in Lamina Propria B Lymphocytes Through TLR4/MyD88/NF-κB Pathway)[J].当代医学科学(英文),2022(05):991-999

Guben,Tongluo,Propria,CD86+CD19+cells,IgAl,Cosmc,CD86+CD19+and

Formula,Protects,LPS,induced,Damage,Lamina,Lymphocytes,Through,TLR4,MyD88,Pathway,Objective,pathological,feature,immunoglobulin,nephropathy,IgAN,autoimmune,kidney,disease,deposition,complexes,accompanied,by,mesangial,proliferation,elevated,urine,protein,formula,GTF,traditional,Chinese,medicine,prescription,which,has,predominant,protective,effects,However,therapeutic,mechanism,remains,elusive,present,study,aimed,determine,treating,via,regulating,pathway,Methods,In,lamina,propria,lymphocytes,were,treated,different,concentrations,lipopolysaccharide,Flow,cytometry,was,used,define,positive,CCK,assay,examine,RNAi,silencing,qRT,blotting,gene,Results,It,found,that,dose,dependently,increased,content,galactose,deficient,Gd,levels,phosphorylated,producing,knockdown,reversed,role,This,suggests,mediates,Furthermore,could,counteract,overexpression,through,Conclusion,Collectively,these,results,demonstrate,can,regulate,model,stimulated

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