title: Reducing progression of experimental lupus nephritis via inhibition of the B7/CD28 signaling pathway.
abstract: The aim of the present study was to evaluate the effects of the B7/cluster of differentiation (CD)28 signaling pathway on experimental lupus nephritis and examine the molecular mechanism involved by inhibiting the B7/CD28 signaling pathway. A lupus nephritis model in C57BL/6 J mice was induced via intraperitoneal injection of pristane. A recombinant B7‑1 short hairpin RNA (shRNA) lentivirus vector was constructed by synthesis and splicing. A neutralizing mouse anti‑human B7‑1 antibody termed 4E5 was also prepared. The mouse model of lupus nephritis was treated with B7‑1 shRNA and 4E5 via injection through the tail vein. The silencing effects of B7‑1 shRNA lentiviral infection on target molecules were evaluated using immunofluorescence and flow cytometry. The levels of protein in the urine were detected using Albustix test paper each month over 10 months. The concentration of interleukin (IL)‑4 and interferon‑γ in the serum was determined using an ELISA. The immune complex (IC) deposits in the kidney were analyzed using direct immunofluorescence. The results demonstrated that the C57BL/6 J mouse lupus nephritis model was successfully constructed with immune cells activated in the spleen of the mice, increases in the concentration of anti‑nuclear antibody (ANA) and anti‑double stranded DNA antibodies as well as positive IC formation. Following B7‑1 shRNA lentivirus or 4E5 treatment, CD11b+B7‑1+, CD11c+B7‑1+ and CD21+B7‑1+ cells in the spleen of the mice were significantly reduced. The concentration of ANA and IL‑4 in the serum was also decreased. The concentration of urine protein was reduced and it was at its lowest level in the 4E5 early intervention group. It was also revealed that the immunofluorescence intensity of the IC deposits was weak in the 4E5 early intervention group. In conclusion, inhibiting the B7‑1/CD28 signaling pathway is able to alleviate experimental lupus nephritis and provides an experimental basis for the therapeutic use of blocking the B7‑1/CD28 signaling pathway in human lupus nephritis and other autoimmune disorders.
authors.affiliation: Department of Internal Medicine, Children's Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Immunology, Medical College, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Laboratory Animal Center of Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Division of Nano Biomedicine, Suzhou Institute of Nano‑Tech and Nano‑Bionics, Chinese Academy of Sciences, Suzhou, Jiangsu 215000, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Immunology, Medical College, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Qiu
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D018122:B7-1 Antigen / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism*; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D020014:K562 Cells; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D016086:Lentivirus / Q000235:genetics; D008181:Lupus Nephritis / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D034622:RNA Interference; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013729:Terpenes / Q000737:chemistry
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D018122:B7-1 Antigen; D018106:CD28 Antigens; D013729:Terpenes; D015847:Interleukin-4; C009042:pristane; D007371:Interferon-gamma