title: Experience with lentivirus-mediated CD40 gene silencing in a mouse model of Graves' disease.
abstract: CD40 plays an important role in the pathogenesis of Graves' disease (GD). Inhibition of CD40 expression may be a promising treatment for GD. In this study, we used an animal model to investigate whether lentivirus expressing siRNA for CD40 (LV-CD40-siRNA) could be useful for the therapy of GD. BALB/c mice were injected with PBS alone (PBS group), negative lentivirus (control siRNA group), or LV-CD40-siRNA (CD40 siRNA group), 3 days before being treated with adenovirus expressing human TSHR A subunit (Ad-TSHR289) three times at 3-week intervals to induce GD model. Sera thyroxine (T(4)) levels were assayed by RIA. The expression of CD40 was detected at the mRNA level by real-time PCR and protein level by flow cytometry. The expression of CD40, CD80, and CD86 was significantly decreased in the CD40 siRNA group (P<0.05), while FOXP3 expression was increased compared to the control siRNA group (P=0.05). Mean T(4) levels were decreased 14% in the CD40 siRNA group compared to the control siRNA group. The rate of disease induction was similar among the three groups injected with Ad-TSHR289. LV-CD40-siRNA is a useful tool to inhibit the expression of CD40 in vivo, but it cannot decrease the incidence of hyperthyroidism in a limited period of time.
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.forename: Bingyin
authors.initials: B
authors.lastname: Shi
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wu
authors.forename: Peng
authors.initials: P
authors.lastname: Hou
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Ma
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Liping
authors.initials: L
authors.lastname: Wu
mesh_terms: D000256:Adenoviridae; D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000235:genetics* / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D020868:Gene Silencing; D005822:Genetic Vectors / Q000276:immunology; D006111:Graves Disease / Q000235:genetics* / Q000276:immunology; D006801:Humans; D016086:Lentivirus; D051379:Mice; D008807:Mice, Inbred BALB C; D034741:RNA, Small Interfering / Q000235:genetics / Q000276:immunology; D011989:Receptors, Thyrotropin / Q000276:immunology / Q000378:metabolism; D013974:Thyroxine / Q000097:blood / Q000276:immunology / Q000378:metabolism
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D034741:RNA, Small Interfering; D011989:Receptors, Thyrotropin; D013974:Thyroxine