title: Bifidobacterium as an oral delivery carrier of interleukin-12 for the treatment of Coxsackie virus B3-induced myocarditis in the Balb/c mice.
abstract: IL-12 plays an important role in the treatment of many infectious diseases by being administered intravenously or intramuscularly. However, intravenous or intramuscular administration is difficult and inconvenient and may cause side effects. The aim of this study is to develop a novel oral delivery system for IL-12 using genetically engineered Bifidobacterium longum as the carrier and further investigate the efficacy of IL-12-expressed B. longum on the coxsackie virus B3 (CVB3)-induced myocarditis in mice. A mIL-12 gene expression vector pBBADs-IL-12 for B. longum was constructed and transformed into Bifidobacterium. Subsequently, the expression of mIL-12 in the engineered B. longum was identified in vitro by western blot and enzyme-linked immunosorbent assay (ELISA) after l-arabinose induction. Moreover, our data indicated that oral administration of IL-12-expressed B. longum for two weeks after CVB3 infection in the Balb/c mice could downregulate the severity of virus-induced myocarditis, markedly reduce the virus titers in the heart and induce a Th1 pattern in the spleen and heart compared with the controls. In conclusion, a novel oral delivery system of Bifidobacterium for murine IL-12 has been successfully established. Oral administration of mIL-12-transformed B. longum may play a therapeutic role in the treatment of CVB3-induced myocarditis in the mice.
authors.affiliation: Department of Infectious Diseases, Shenzhen Nanshan People's Hospital, Guangdong Medical College, Shenzhen, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Yu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.forename: Chongwen
authors.initials: C
authors.lastname: Sao
authors.forename: Yuanjian
authors.initials: Y
authors.lastname: Huang
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
authors.forename: Jie
authors.initials: J
authors.lastname: Lian
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zeng
authors.forename: Wenshen
authors.initials: W
authors.lastname: Luo
authors.forename: Weiseng
authors.initials: W
authors.lastname: Zeng
authors.forename: Qiwen
authors.initials: Q
authors.lastname: Deng
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001644:Bifidobacterium / Q000235:genetics*; D003384:Coxsackievirus Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004337:Drug Carriers / Q000008:administration & dosage*; D005243:Feces / Q000737:chemistry; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000097:blood / Q000235:genetics; D007963:Leukocytes, Mononuclear; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000235:genetics; D014169:Transformation, Bacterial; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D004337:Drug Carriers; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma