Recent genome-wide association studies suggest distinct roles for 12 human interferon-alpha (IFN-α) and 3 IFN-λ subtypes that may be elucidated by defining the expression patterns of these sets of genes. To overcome the impediment of high homology among each of the sets, we designed a quantitative real-time PCR assay that incorporates the use of molecular beacon and locked nucleic acid (LNA) pr...

TLR9 recognizes DNA sequences containing hypomethylated CpG motifs and is a component of the innate immune system highly conserved during eukaryotic evolution. Previous reports suggested that the expression of TLR9 is restricted to plasmacytoid dendritic cells and B lymphocytes. Our results indicate that low levels of TLR9 are present on the cell surface of freshly isolated human monocytes, and...

Pseudomonas aeruginosa is a critical colonizer of the respiratory tract in cystic fibrosis. The chronic infections with this microorganism contribute to excessive inflammation and progressive lung damage in cystic fibrosis patients. The full repertoire of Pseudomonas products that promote inflammation in the cystic fibrosis lung is not known. Here we show that P. aeruginosa DNA released from th...

A20 is an ubiquitin-editing enzyme that ensures the transient nature of inflammatory signaling pathways induced by cytokines like TNF-α and IL-1 or pathogens via Toll-like receptor (TLR) pathways. It has been identified as a negative regulator of dendritic cell (DC) maturation and attenuator of their immunostimulatory properties. Ex vivo A20-depleted dendritic cells showed enhanced expression o...

CpG oligodeoxynucleotides (ODN) show promise as immunoprotective agents and vaccine adjuvants. CpG ODN type D were shown to improve clinical outcome in rhesus macaques challenged with Leishmania major. These ODN have a self-complementary core sequence and a 3' end poly(G) track that favors G-tetrad formation leading to multimerization. Although multimerization appears necessary for localization...

The present study demonstrates the efficacy of utilizing TLR9 (toll-like receptor 9) agonism as a potential therapy for colon cancer. We examined the effects of two types of TLR9 agonists: a traditional CpG oligonucleotide and a novel immunomodulatory oligonucleotide in models of colon cancer, both alone and in combination with conventional cancer therapies. Because the tumor suppressor p53 is ...

Despite significant advances in the access control domain, requirements of new computational environments like web services still raise new challenges. Lack of appropriate method for specification of access control policies (ACPs), composition, verification and analysis of them have all made the access control in the composition of web services a complicated problem. In this paper, a new indepe...

There is a potential role for antisense oligonucleotides in the treatment of disease. The principle of antisense technology is the sequence-specific binding of an antisense oligonucleotide to target mRNA, resulting in the prevention of gene translation. The specificity of hybridisation makes antisense treatment an attractive strategy to selectively modulate the expression of genes involved in t...

31P cross polarization (CP) magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectra were acquired for various linear and branched di- and tri-nucleotides attached to a controlled pore glass (CPG) solid support. The technique readily distinguishes the oxidation state of the phosphorus atom (phosphate versus phosphate), the presence or absence of a protecting group attached directly t...

OBJECTIVE Mitochondrial transcription factor A (TFAM) is normally bound to and remains associated with mitochondrial DNA (mtDNA) when released from damaged cells. We hypothesized that TFAM, bound to mtDNA (or equivalent CpG-enriched DNA), amplifies TNFα release from TLR9-expressing plasmacytoid dendritic cells (pDCs) by engaging RAGE. MATERIALS AND METHODS Murine Flt3 ligand-expanded splenocy...