title: Amiloride enhances antigen specific CTL by faciliting HBV DNA vaccine entry into cells.
abstract: The induction of relatively weak immunity by DNA vaccines in humans can be largely attributed to the low efficiency of transduction of somatic cells. Although formulation with liposomes has been shown to enhance DNA transduction of cultured cells, little, if any, effect is observed on the transduction of somatic tissues and cells. To improve the rate of transduction, DNA vaccine delivery by gene gun and the recently developed electroporation techniques have been employed. We report here that to circumvent requirement for such equipment, amiloride, a drug that is prescribed for hypertension treatment, can accelerate plasmid entry into antigen presenting cells (APCs) both in vitro and in vivo. The combination induced APCs more dramatically in both maturation and cytokine secretion. Amiloride enhanced development of full CD8 cytolytic function including induction of high levels of antigen specific CTL and expression of IFN-γ+perforin+granzymeB+ in CD8+ T cells. Thus, amiloride is a facilitator for DNA transduction into host cells which in turn enhances the efficiency of the immune responses.
authors.affiliation: Key laboratory of Medical Molecular Virology of MOH and MOE, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Geng
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Zhong
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Hu
authors.initials: H
authors.lastname: Liu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zou
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xie
authors.forename: Chaofan
authors.initials: C
authors.lastname: Li
authors.forename: Qingling
authors.initials: Q
authors.lastname: Yu
authors.forename: Zhonghuai
authors.initials: Z
authors.lastname: He
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D005260:Female; D053804:Granzymes / Q000378:metabolism; D017325:Hepatitis B Vaccines / Q000235:genetics / Q000276:immunology* / Q000493:pharmacokinetics; D007111:Immunity, Cellular / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010957:Plasmids / Q000235:genetics / Q000493:pharmacokinetics; D052899:Pore Forming Cytotoxic Proteins / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D014161:Transduction, Genetic; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000493:pharmacokinetics
chemical_list: D017325:Hepatitis B Vaccines; D052899:Pore Forming Cytotoxic Proteins; D026941:Sodium Channel Blockers; D019444:Vaccines, DNA; C483886:perforin, mouse; D000584:Amiloride; D007371:Interferon-gamma; D053804:Granzymes; C509214:Gzmb protein, mouse