8 Br-cAMP enhances both humoral and cell-mediated immune responses induced by an HIV-1 DNA vaccine

Arai, Hiroyuki; Kq, Xin; Hamajima, Kenji; Lu, Yue; Watabe, Setsuko; Takahashi, Toru; Toda, Soji; Okuda, K; Kudoh, Ichidai; Suzuki, Motoyoshi

doi:10.1038/sj.gt.3301145

Cited by 5 publications

(3 citation statements)

References 44 publications

(38 reference statements)

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“…Instead of using the NIS promoter, we used a murine CMV promoter in this experiment for ectopic expression of hNIS/tdTomato without TSH. However, the CMV promoter also activated by cAMP [ 38 , 39 ]. Therefore, the localization of hNIS/tdTomato should be measured in the absence of cAMP-induced de novo hNIS protein synthesis.…”

Section: Resultsmentioning

confidence: 99%

Glycosylation of Sodium/Iodide Symporter (NIS) Regulates Its Membrane Translocation and Radioiodine Uptake

et al. 2015

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PurposeHuman sodium/iodide symporter (hNIS) protein is a membrane glycoprotein that transports iodide ions into thyroid cells. The function of this membrane protein is closely regulated by post-translational glycosylation. In this study, we measured glycosylation-mediated changes in subcellular location of hNIS and its function of iodine uptake.MethodsHeLa cells were stably transfected with hNIS/tdTomato fusion gene in order to monitor the expression of hNIS. Cellular localization of hNIS was visualized by confocal microscopy of the red fluorescence of tdTomato. The expression of hNIS was evaluated by RT-PCR and immunoblot analysis. Functional activity of hNIS was estimated by radioiodine uptake. Cyclic AMP (cAMP) and tunicamycin were used to stimulate and inhibit glycosylation, respectively. In vivo images were obtained using a Maestro fluorescence imaging system.ResultscAMP-mediated Glycosylation of NIS resulted in increased expression of hNIS, stimulating membrane translocation, and enhanced radioiodine uptake. In contrast, inhibition of glycosylation by treatment with tunicamycin dramatically reduced membrane translocation of intracellular hNIS, resulting in reduced radioiodine uptake. In addition, our hNIS/tdTomato fusion reporter successfully visualized cAMP-induced hNIS expression in xenografted tumors from mouse model.ConclusionsThese findings clearly reveal that the membrane localization of hNIS and its function of iodine uptake are glycosylation-dependent, as our results highlight enhancement of NIS expression and glycosylation with subsequent membrane localization after cAMP treatment. Therefore, enhancing functional NIS by the increasing level of glycosylation may be suggested as a promising therapeutic strategy for cancer patients who show refractory response to conventional radioiodine treatment.

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Section: Resultsmentioning

confidence: 99%

Glycosylation of Sodium/Iodide Symporter (NIS) Regulates Its Membrane Translocation and Radioiodine Uptake

et al. 2015

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“…The CMV promoter, responsive to cAMP, was activated by addition of 8 Br-cAMP increasing the immune response to the respective antigen HIV-1 gp160 [112].…”

Section: Promotersmentioning

confidence: 99%

Update on Antiviral DNA Vaccine Research (1998–2000)

2000

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DNA vaccines can induce protective cellular and humoral immune responses and have therefore been used during the last decade to develop vaccines against a variety of different pathogens. Because current antiviral vaccines predominantly generate humoral immunity, DNA immunization may be especially useful to provide long-term protection against viral diseases that also require cellular immunity (e.g. HIV). A significant number of articles published in the field of DNA vaccines are dealing with viral diseases, reflecting the need for better and alternative vaccination strategies against viruses. The success of DNA immunization depends on a variety of parameters (e.g. type of antigen, method of application and usage of adjuvants). Therefore, different strategies have been explored to modulate the induced immune response with respect to the requirements necessary to protect against a specific pathogen (e.g. induction of mucosal or cell-mediated immunity). The following article provides an update on different aspects of antiviral DNA vaccine research that have previously been reviewed by others.

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“…Arai et al [ 54 ] examined the adjuvant effect of 8-bromocyclic AMP (8 Br-cAMP) on an HIV-1 DNA vaccine. Administration of the DNA vaccine and 8 Br-cAMP combination, via i.m.…”

Section: Enhancing the Methods Of Dna Vaccinationmentioning

confidence: 99%

Recent Developments in Preclinical DNA Vaccination

Okuda

Wada²,

Shimada

2014

Vaccines

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The advantages of genetic immunization of the new vaccine using plasmid DNAs are multifold. For example, it is easy to generate plasmid DNAs, increase their dose during the manufacturing process, and sterilize them. Furthermore, they can be stored for a long period of time upon stabilization, and their protein encoding sequences can be easily modified by employing various DNA-manipulation techniques. Although DNA vaccinations strongly increase Th1-mediated immune responses in animals, several problems persist. One is about their weak immunogenicity in humans. To overcome this problem, various genetic adjuvants, electroporation, and prime-boost methods have been developed preclinically, which are reviewed here.

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8 Br-cAMP enhances both humoral and cell-mediated immune responses induced by an HIV-1 DNA vaccine

Cited by 5 publications

References 44 publications

Glycosylation of Sodium/Iodide Symporter (NIS) Regulates Its Membrane Translocation and Radioiodine Uptake

Glycosylation of Sodium/Iodide Symporter (NIS) Regulates Its Membrane Translocation and Radioiodine Uptake

Update on Antiviral DNA Vaccine Research (1998–2000)

Recent Developments in Preclinical DNA Vaccination

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