Browsing by Subject "Mice, Inbred C57BL"

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Open Access
Enhanced immunostimulatory activity of cyclic dinucleotides on mouse cells when complexed with a cell-penetrating peptide or combined with CpG
(Wiley - V C H Verlag GmbH & Co. KGaA, 2015) Yildiz, S.; Alpdundar, E.; Gungor, B.; Kahraman, T.; Bayyurt, B.; Gursel, I.; Gursel, M.
Recognition of pathogen-derived nucleic acids by immune cells is critical for the activation of protective innate immune responses. Bacterial cyclic dinucleotides (CDNs) are small nucleic acids that are directly recognized by the cytosolic DNA sensor STING (stimulator of IFN genes), initiating a response characterized by proinflammatory cytokine and type I IFN production. Strategies to improve the immune stimulatory activities of CDNs can further their potential for clinical development. Here, we demonstrate that a simple complex of cylic-di-GMP with a cell-penetrating peptide enhances both cellular delivery and biological activity of the cyclic-di-GMP in murine splenocytes. Furthermore, our findings establish that activation of the TLR-dependent and TLR-independent DNA recognition pathways through combined use of CpG oligonucleotide (ODN) and CDN results in synergistic activity, augmenting cytokine production (IFN-α/β, IL-6, TNF-α, IP-10), costimulatory molecule upregulation (MHC class II, CD86), and antigen-specific humoral and cellular immunity. Results presented herein indicate that 3′3′-cGAMP, a recently identified bacterial CDN, is a superior stimulator of IFN genes ligand than cyclic-di-GMP in human PBMCs. Collectively, these findings suggest that the immune-stimulatory properties of CDNs can be augmented through peptide complexation or synergistic use with CpG oligonucleotide and may be of interest for the development of CDN-based immunotherapeutic agents.
Open Access
Strain-and region-specific gene expression profiles in mouse brain in response to chronic nicotine treatment
(Wiley-Blackwell Publishing, 2008) Wang, J.; Gutala, R.; Hwang, Y. Y.; Kim J. -M.; Konu, O.; Ma, J. Z.; Li, M. D.
A pathway-focused complementary DNA microarray and gene ontology analysis were used to investigate gene expression profiles in the amygdala, hippocampus, nucleus accumbens, prefrontal cortex (PFC) and ventral tegmental area of C3H/HeJ and C57BL/6J mice receiving nicotine in drinking water (100 μg/ml in 2% saccharin for 2 weeks). A balanced experimental design and rigorous statistical analysis have led to the identification of 3.5-22.1% and 4.1-14.3% of the 638 sequence-verified genes as significantly modulated in the aforementioned brain regions of the C3H/HeJ and C57BL/6J strains, respectively. Comparisons of differential expression among brain tissues showed that only a small number of genes were altered in multiple brain regions, suggesting presence of a brain region-specific transcriptional response to nicotine. Subsequent principal component analysis and Expression Analysis Systematic Explorer analysis showed significant enrichment of biological processes both in C3H/HeJ and C57BL/6J mice, i.e. cell cycle/proliferation, organogenesis and transmission of nerve impulse. Finally, we verified the observed changes in expression using real-time reverse transcriptase polymerase chain reaction for six representative genes in the PFC region, providing an independent replication of our microarray results. Together, this report represents the first comprehensive gene expression profiling investigation of the changes caused by nicotine in brain tissues of the two mouse strains known to exhibit differential behavioral and physiological responses to nicotine.