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Held Katherine S KS Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697-3900, - - 2008
The functional role of IL-12 and IL-23 in host defense and disease following viral infection of the CNS was determined. Instillation of mouse hepatitis virus (MHV, a positive-strand RNA virus) into the CNS of mice results in acute encephalitis followed by a chronic immune-mediated demyelinating disease. Antibody-mediated blocking of either ...
Zhang Sheng - - 2008
IL-12 is an important type 1 immune activation cytokine. It is known that macrophages and dendritic cells the major cell types producing this cytokine and that these cells may release both the biologically inactive form (IL-12p40) and active form (IL-12p70) of IL-12. In this review, the latest information regarding the ...
Blum Arthur - - 2008
Substance P is a tachykinin that enhances pathways of inflammation. Leukocytes at sites of intestinal inflammation make substance P. This study explored the role of interleukin-12 (IL-12), IL-23, and the regulatory cytokines IL-10 and transforming growth factor beta (TGF-beta) in controlling leukocyte substance P production. In murine schistosomiasis, it was ...
Wang Junpeng - - 2008
Cimetidine (CIM), a histamine 2-receptor antagonist, is postulated to enhance immune responses owing to its inhibitory effects on suppressor T cells. In this report, we evaluated effects of cimetidine on the potency of antigen-specific immunity generated by DNA vaccine encoding hepatitis B surface antigen (HBsAg, pcD-S2). Our data demonstrate that ...
Gerosa Franca - - 2008
We analyzed interleukin (IL) 12 and IL-23 production by monocyte-derived dendritic cells (mono-DCs). Mycobacterium tuberculosis H37Rv and zymosan preferentially induced IL-23. IL-23 but not IL-12 was efficiently induced by the combination of nucleotide-binding oligodimerization domain and Toll-like receptor (TLR) 2 ligands, which mimics activation by M. tuberculosis, or by the ...
Klinman Dennis - - 2008
Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs mimic the immunostimulatory activity of bacterial DNA. CpG ODN directly stimulate human B cells and plasmacytoid dendritic cells, promote the production of Th1 and proinflammatory cytokines, and trigger the maturation/activation of professional APC. CpG ODN are finding use in the treatment of cancer, ...
Ramirez-Ortiz Zaida G ZG Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, MA 01605, - - 2008
Phagocytic defenses are critical for effective host defenses against the opportunistic fungal pathogen Aspergillus fumigatus. Previous studies found that following challenge with A. fumigatus, Toll-like receptor 9 (TLR9) knockout mice survived longer than wild-type mice. However, the mechanism responsible was not defined. Here we demonstrate that A. fumigatus contains unmethylated ...
Butchar Jonathan P JP Division of Pulmonary and Critical Care, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, - - 2008
We previously demonstrated that monocytes produce IL-23 during Francisella infection, and that IL-23 induces IFNgamma from NK cells. Here, we demonstrate that IFNgamma-priming of monocytes enhances IL-23 production during Francisella infection. This effect was seen on the IL12/23 p40 subunit. Induction of IL-12/23 p40 is reported to be enhanced by ...
Mousavi Tahereh - - 2008
BACKGROUND: There are many therapeutic methods for allergic conditions. CpG oligonucleotides play a critical role in immunity via the augmentation of Th1 and suppression of Th2 responses. OBJECTIVE: In the present study we aimed to estimate the effectiveness of intranasal administration of CpG ODN plus Chenopodium album allergen in allergic ...
Xiao Gang - - 2008
Cryptococcus neoformans is eradicated by macrophages via production of NO. Unmethylated CpG-ODN protect mice from infection with this fungal pathogen by inducing IFN-gamma. The present study was designed to elucidate the effect of C. neoformans on the synthesis of NO by alveolar macrophages. For this purpose, MH-S, an alveolar macrophage ...
Wang, Mingyue
Abstract Background We have previously shown that supernatant from Candida albicans (CA) culture contains a Secretory Interleukin (IL)-12 Inhibitory Factor (CA-SIIF), which inhibits IL-12 production by human monocytes. However, the effect of CA-SIIF on secretion of other cytokines by monocytes is unknown, and detailed characterization of this factor has not ...
de Jong, Susan Rachel ...
Immunostimulatory oligodeoxynucleotides (ODN) containing unmethylated CpG motifs are powerful stimulators of innate as well as adaptive immune responses, exerting their activity through the triggering of the endosomally localized TLR9 by a poorly understood mechanism. The immunopotency and broad range of activity of CpG ODN makes it a promising immunotherapeutic for ...
Rutitzky Laura I - - 2008
In infection with the trematode helminth Schistosoma mansoni, the severity of CD4 T cell-mediated hepatic granulomatous and fibrosing inflammation against parasite eggs varies considerably in humans and among mouse strains. In mice, either the natural high pathology, or high pathology induced by concomitant immunization with schistosome egg Ags (SEA) in ...
Goriely Stanislas - - 2008
PURPOSE OF REVIEW: Allograft rejection involves multiple effector mechanisms. Interleukin(IL)-12 family members play a critical role in influencing helper T-cell differentiation and inflammatory processes, and their respective role in orchestrating inflammation of autoimmune or infectious origin starts to be unravelled. We highlight recent findings on the function of the different ...
Gray, Reginald Courtney
Deoxycytidyl-deoxyguanosine (CpG) oligodeoxynucleotides (ODNs) are single strands of synthetic DNA that mimic bacterial and viral DNA. CpG ODNs are divided into three classes (CpG-A, -B, and -C), which differ in their sequence characteristics and immunomodulatory functions. All three classes signal through TLR9. TLRs and other pattern recognition receptors are under ...
Goriely Stanislas - - 2008
Interleukin-12p70 (IL-12p70) induces T-helper-1-cell responses and IL-23, a related cytokine, is the master switch in several T-cell-mediated inflammatory disorders. IL-27, another member of the IL-12 family, regulates innate and adaptive immune responses. Recently, distinct combinations of transcription factors have been shown to regulate the expression of the genes that encode ...
Conte Enrico - - 2008
The heterodimeric cytokine IL-12 (composed of a p35 and a p40 subunit) is produced primarily by monocytes, macrophages and B cells. In vitro and in vivo experiments have demonstrated the crucial role of IL-12 in initiating and establishing both innate immunity and T cell-mediated resistance to intracellular pathogens, including Leishmania ...
Hemdan Nasr Ya - - 2008
Increasing evidence exists that heavy metals modulate T helper cell (Th) responses and thereby elicit various pathological manifestation. Interleukin (IL)-12, a crucial innate cytokine, was found to be regulated by such xenobiotic agents. This study aimed at testing whether IL-12 profiles may be indicative of heavy metals-induced immunomodulation. Human immunocompetent ...
Takagi Hideaki - - 2007
The present study demonstrates that liposomes coated with synthesized neoglycolipids constructed from mannotriose and dipalmitoylphosphatidylethanolamine (Man3-DPPE) activate peritoneal macrophages (PEMs) to up-regulate expression of co-stimulatory molecules and preferentially secrete IL-12. Injection of Man3-DPPE-coated liposomes (oligomannose-coated liposome, OMLs) into the peritoneal cavity of mice resulted in specific and rapid incorporation of ...
Johnson, Jolyn
The innate immune system is an important mechanism that protects the host from infection. Viral and bacterial infection triggers activation of the transcription factors interferon response factor (IRF) 3 and nuclear factor (NF)-kB. These transcription factors collaborate to induce transcription of type I interferons (IFNs) cytokines and the interleukin (IL)-12 ...
Chuang Lisa - - 2007
It is believed that probiotics play an important role for the health of the host, including modulation of immune responses. Most studies have focused on the immunomodulatory effects of viable cells of lactic acid bacteria; however, we investigated those of heat-killed cells of lactic acid bacteria in this study. We ...
Xu Wen - - 2008
Allergic inflammation is induced by type 2 T helper cell (Th2) and Th2 cytokines such as interleukin (IL)-4, IL-5 and IL-13. These cytokines induce the production of allergen-specific immunoglobulin (Ig)E by B cells, and the ensuing degranulation of mast cells via IgE cross-linking leads to most clinical manifestations of allergic ...
Secchiero Paola - - 2008
We have investigated the effect of combined treatment with CpG-oligodeoxynucleotide (CpG-ODN) plus Nutlin-3, a small molecule inhibitor of the murine double minute 2/p53 interaction, on the immune activation, cell cycle progression, and apoptosis of peripheral blood B chronic lymphocytic leukemia (B-CLL) cells. CpG-ODN induced a robust up-regulation of immune activation ...
Peter Mirjam - - 2008
Synthetic oligodeoxynucleotides containing unmethylated CpG sequences (CpG-ODNs) stimulate Toll-like receptor-9 (TLR-9), thereby activating innate immunity. Stimulatory CpG-ODNs have been shown to be valuable in modifying immune responses in allergy, infection and cancer. Recently, it has been reported that the stimulation of TLR-9 by endogenous DNA might contribute to the pathogenesis ...
Sathler-Avelar Renato - - 2008
Pro-inflammatory immune response is usually associated with Chagas disease pathogenesis, but is also relevant to treatment effectiveness. Cross-sectional studies have suggested that this activated state may persist for years after therapeutic intervention. However, short-term longitudinal investigation has suggested that the Benznidazole treatment (Bz-treatment) leads to decreased immunological activation. In order ...
Becskei Attila - - 2007
T helper 1 (Th1) cell fate is induced by overlapping signaling pathways, whose kinetic principles and regulatory motifs are largely unknown. We identified a simple positive feedback loop in the STAT4 signaling pathway, whereby activation by IL-12 leads to the increased expression in IL-12 receptor. A computational analysis shows that ...
Oganesyan Gagik - - 2008
Hypomethylated CpG oligonucleotides (CpG) are not only potent adjuvants for enhancing adaptive immune responses but may also play a critical role in the development of autoimmune diseases such as Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE). Here we provide evidence that, in addition to dendritic cells, murine B lymphocytes ...
Matsui Masanori - - 2007
Interleukin (IL)-12 is a heterodimeric proinflammatory cytokine formed by a 35-kDa light chain (p35) and a 40-kDa heavy chain (p40). This cytokine is a key regulator of cell-mediated immunity, and therefore should have therapeutic potential in infectious diseases and tumors. Recently, a novel IL-12-associated cytokine, IL-23 has been discovered. IL-23 ...
Sharma Sanjay - - 2008
AIM: There is accumulative evidence indicating that targeting antigen presenting cells (APCs) with different types of adjuvants could result in the induction of antitumor immune responses. It has been hypothesized that APCs function may be altered in the elderly contributing to a decline in the immune function. We evaluated whether ...
Kaiser-Schulz Gunnar - - 2007
Prion diseases are fatal neurodegenerative diseases that are characterized by the conformational conversion of the normal, mainly alpha-helical cellular prion protein (PrP) into the abnormal beta-sheet-rich infectious isoform (PrP(Sc)). The immune system neither shows reaction against cellular PrP nor PrP(Sc), most likely due to profound self-tolerance. In previous studies, we ...
Hasan Maroof - - 2008
Bruton's tyrosine kinase (Btk), a member of the Tec family of tyrosine kinases, plays an important role in the differentiation and activation of B cells. Mutations affecting Btk cause immunodeficiency in both humans and mice. In this study we set out to investigate the potential role of Btk in Toll-like ...
Del Vecchio Michele - - 2007
Interleukin-12 (IL-12) is a heterodimeric protein, first recovered from EBV-transformed B cell lines. It is a multifunctional cytokine, the properties of which bridge innate and adaptive immunity, acting as a key regulator of cell-mediated immune responses through the induction of T helper 1 differentiation. By promoting IFN-gamma production, proliferation, and ...
Chang Hyun-Dong - - 2007
T helper (Th) lymphocytes, upon activation and differential costimulation, differentiate into various types of Th memory cells with distinct functions. Upon activation in the presence of interleukin-12 (IL-12), Th1 memory cells are imprinted for the expression of interferon-gamma (IFN-gamma), by genetic modification of the ifngamma gene and expression of the ...
Ratanamart Jarupa - - 2007
BACKGROUND: Plasmid DNA vectors offer the potential of safe gene therapy avoiding viral vector-mediated toxicity and immunogenicity. As plasmid DNA is bacterial in origin, presence of bacterial lipopolysaccharide (LPS) or unmethylated CpG dinucleotides may stimulate host innate immunity. METHODS: Primary cultures of mouse and rat dendritic cells were established and ...
Blanks Deidra A - - 2007
PURPOSE OF REVIEW: To review the current literature regarding immunostimulatory sequences of DNA for immunotherapy with respect to signaling mechanisms, cytokine profiles, structural characteristics and the applicability and success of this strategy to treat allergic disease. RECENT FINDINGS: The binding of synthetic DNA-based immunotherapy agents composed of unmethylated cytosine-guanine dinucleotides ...
Robinson T M - - 2007
BACKGROUND: The cell mediated immune profiles following immunization with a recombinant DNA vaccine was assessed in the simian-human immunodeficiency virus (SHIV) and Macaque model. Earlier work demonstrated increased numbers of antigen specific CD8 and CD4 effector cells able to secrete IFN-gamma. METHOD: The vaccine strategy included co-immunization of a DNA ...
Wu Hsin-Jung - - 2007
Unmethylated CpG-oligodeoxynucleotides (ODNs) are generally thought of as potent adjuvants with considerable therapeutic potential to enhance immune responses against microbes and tumors. Surprisingly, certain so-called stimulatory CpG-ODNs strongly inhibited the effector phase of inflammatory arthritis in the K/BxN serum transfer system, either preventively or therapeutically. Also unexpected was that the ...
Sinha Pratima - - 2007
Although the immune system has the potential to protect against malignancies, many individuals with cancer are immunosuppressed. Myeloid-derived suppressor cells (MDSC) are elevated in many patients and animals with tumors, and contribute to immune suppression by blocking CD4(+) and CD8(+) T cell activation. Using the spontaneously metastatic 4T1 mouse mammary ...
Neufert Clemens - - 2007
IL-27 is an IL-12-related cytokine frequently present at sites of inflammation that can promote both anti- and pro-inflammatory immune responses. Here, we have analyzed the mechanisms how IL-27 may drive such divergent immune responses. While IL-27 suppressed the development of proinflammatory Th17 cells, a novel role for this cytokine in ...
Fan Timothy M - - 2007
With respect to CD8 effector T cells, interleukin-12 (IL-12) and transforming growth factor beta (TGFbeta) are 2 cytokines that exert opposing effects. IL-12 promotes antitumor immune responses by augmenting activated CD8 T-cell proliferation and interferon-gamma secretion. Conversely, TGFbeta generates a permissive environment for cancer growth, in part by antagonizing the ...
Wang Jinhai - - 2007
Ag presentation is a key step in the initiation of adaptive immune responses that depends on the expression of MHC Ags and costimulatory molecules. Immune-enhancing CpG and non-CPG oligodeoxynucleotides (ODNs) stimulate Ag presentation by stimulating the expression of these molecules and by promoting dendritic cell maturation. In this report, we ...
Merlo Andrea - - 2007
The recognition of pathogen-associated molecular patterns by TLRs triggers the activation of innate and adaptive immune responses. Flagellin, the agonist of TLR5, is expressed by prokaryotes and eukaryotes, and DNA sequences containing unmethylated CpG dinucleotides, agonists of TLR9, are present essentially in prokaryotes. To test the potential modulating effects of ...
Ikeda Masato - - 2007
A cationic polysaccharide bearing a beta-1,3-glucan main-chain structure (CUR-N(+)) forms a complex with a hetero-sequence oligonucleotide, that is, a CpG ODN, and facilitates the transportation of the resultant complex into a murine macrophage-like cell J774.A1, which induces an efficient secretion of a cytokine (IL-12) as compared with that induced by ...
Rosa Daniela Santoro - - 2007
Synthetic oligonucleotides (ODNs) containing immunostimulatory CpG motifs (CpG) are a new class of adjuvants suitable for the development of recombinant vaccines. Here we describe that endogenous interferon (IFN) was critical for the adjuvant activity of CpG ODN as genetically deficient mice developed significantly lower IgG antibody titers following immunization with ...
Hadidi, Sima
The aim of the present study was to elucidate the role of regulatory type 1 cytokines, particularly IL-12 and IFN-[gamma] in the mechanisms by which the immune responses are suppressed or augmented. The hypothesis was that in patients with CRF, impaired immunity is caused by a defective T cell activation ...
Kuo Cheng-Chin - - 2007
Unmethylated CpG oligodeoxynucleotides (CpG ODNs) activate immune responses in a TLR9-dependent manner. In this study, we found that stimulation of mouse macrophages and dendritic cells with B-type CpG ODN (CpG-B ODN) increased the cellular level of heat shock protein (Hsp) 90beta but not Hsp90alpha and prevented apoptosis induced by serum ...
Bashyam Hema - - 2007
Early resistance to pathogens requires a swift response from NK cells. In 1989, Giorgio Trinchieri identified an NK growth factor and activator, later called interleukin-12 (IL-12). This discovery helped reveal the regulatory link between innate and adaptive immunity.
Wilson Kaley D - - 2007
We have previously demonstrated that the immune response to an unmethylated cytidine-guanosine (CpG)-containing oligonucleotide (ODN) is greatly enhanced when encapsulated in a lipid nanoparticle (LN-CpG ODN). In this study, the pharmacokinetics, biodistribution and cellular uptake of LN-CpG ODN following intravenous (i.v.) and subcutaneous (s.c.) administration was characterized and correlated with ...
Klinke David J DJ - - 2007
Health Sciences face a significant challenge in translating basic science data into improved understanding of innate and adaptive immunity. To improve understanding of the dynamic role of dendritic cells in the lung, a mathematical model was developed using a physiologically structured framework that explicitly accounts for functional heterogeneity. As sentinels ...
Knauer Jens - - 2007
Lyme borreliosis is characterized by cellular inflammatory responses at multiple body sites. Recently, an association of interleukin-17 (IL-17) and Lyme arthritis was suggested. In this context, it is of special interest that the heterodimeric cytokine IL-23 can act on T cells and initiate the up-regulation of effector cytokines such as ...
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