PMC:17824 / 4572-7202
Annnotations
2_test
{"project":"2_test","denotations":[{"id":"11178126-8610135-4389664","span":{"begin":416,"end":417},"obj":"8610135"},{"id":"11178126-9645386-4389665","span":{"begin":418,"end":419},"obj":"9645386"},{"id":"11178126-9247576-4389666","span":{"begin":420,"end":421},"obj":"9247576"},{"id":"11178126-8610135-4389667","span":{"begin":498,"end":499},"obj":"8610135"},{"id":"11178126-1376349-4389668","span":{"begin":500,"end":501},"obj":"1376349"},{"id":"11178126-8757300-4389669","span":{"begin":502,"end":503},"obj":"8757300"},{"id":"11178126-2423876-4389670","span":{"begin":662,"end":663},"obj":"2423876"},{"id":"11178126-2352943-4389671","span":{"begin":664,"end":665},"obj":"2352943"},{"id":"11178126-2423876-4389672","span":{"begin":840,"end":841},"obj":"2423876"},{"id":"11178126-2352943-4389673","span":{"begin":842,"end":843},"obj":"2352943"},{"id":"11178126-7700380-4389674","span":{"begin":964,"end":965},"obj":"7700380"},{"id":"11178126-8885863-4389675","span":{"begin":966,"end":967},"obj":"8885863"},{"id":"11178126-10371511-4389676","span":{"begin":1056,"end":1058},"obj":"10371511"},{"id":"11178126-10371511-4389677","span":{"begin":1839,"end":1841},"obj":"10371511"},{"id":"11178126-8717520-4389678","span":{"begin":2135,"end":2137},"obj":"8717520"},{"id":"11178126-8977288-4389679","span":{"begin":2144,"end":2146},"obj":"8977288"},{"id":"11178126-8651990-4389680","span":{"begin":2160,"end":2162},"obj":"8651990"},{"id":"11178126-3805716-4389681","span":{"begin":2280,"end":2282},"obj":"3805716"},{"id":"11178126-3140821-4389682","span":{"begin":2283,"end":2285},"obj":"3140821"},{"id":"11178126-9379000-4389683","span":{"begin":2286,"end":2288},"obj":"9379000"},{"id":"11178126-9834074-4389684","span":{"begin":2289,"end":2291},"obj":"9834074"},{"id":"11178126-9536122-4389685","span":{"begin":2292,"end":2294},"obj":"9536122"}],"text":"Introduction\nSeveral reports on the immunostimulatory properties of bacterial DNA have recently been published. Bacterial DNA directly activates B cells, monocytes, macrophages, and dendritic cells in vitro to upregulate their expression of costimulatory molecules that drive immune responses and secrete a variety of cytokines, including high levels of interleukin (IL)-12, IL-1, and tumor necrosis factor (TNF)-α [1,2,3]. Bacterial DNA indirectly activates natural killer (NK) cells and T cells [1,4,5], whereas vertebrate DNA lacks immunostimulatory effects. Unmethylated CpG motifs are common in bacterial DNA and considerably less common in vertebrate DNA [6,7]. In addition, whereas CpG motifs in bacterial DNA are unmethylated, the great majority of C and G nucleotides are methylated in all eukaryotic organisms, including mammals [6,7]. Unmethylated CpG oligodinucleotides (CpG ODNs) are responsible for the immunostimulatory properties of bacterial DNA [8,9].\nOur group has recently reported that intra-articular bacterial DNA induces arthritis [10]. Histopathological signs of the arthritis were evident within two hours and lasted for at least three weeks, and it was characterized by an influx of monocytic, Mac-1+ cells and a scarcity of T lymphocytes. Unmethylated CpG motifs were responsible for the induction of this arthritis. This proinflammatory effect of bacterial DNA did not appear to be caused by contamination with endotoxins, since mice that did not respond to lipopolysaccharides developed arthritis in response to CpG ODNs but not in response to non-DNA bacterial contamination. Neither T cells, B cells, NK cells, nor neutrophils were found to be mandatory for induction of CpG ODN-mediated arthritis, whereas macrophages played a major role in induction of arthritis triggered by CpG motifs in bacterial DNA [10].\nCytokines have been shown to exert an important role in the pathogenesis of arthritis in several mouse models. TNF-α, IL-1β, IFN-γ, and IL-12 are all produced in various quantities in the joints of patients with rheumatoid arthritis and in experimental arthritides such as collagen-induced [11,12,13,14] and septic [15] arthritis. These cytokines play an important role in the induction and development of aseptic and septic arthritis [16,17,18,19,20]. To better understand the pathogenesis of CpG ODN-mediated arthritis, we wanted to know more about the expression and role of these cytokines during its early phase. We therefore investigated the patterns of local cytokine mRNA using hybridization in situ and assessed the role of IL-12 in the induction of CpG ODN-mediated arthritis."}
Colil
{"project":"Colil","denotations":[{"id":"T5","span":{"begin":418,"end":419},"obj":"9645386"},{"id":"T6","span":{"begin":420,"end":421},"obj":"9247576"},{"id":"T7","span":{"begin":2286,"end":2288},"obj":"9379000"},{"id":"T8","span":{"begin":662,"end":663},"obj":"2423876"},{"id":"T9","span":{"begin":664,"end":665},"obj":"2352943"},{"id":"T10","span":{"begin":498,"end":499},"obj":"8610135"},{"id":"T11","span":{"begin":500,"end":501},"obj":"1376349"},{"id":"T12","span":{"begin":502,"end":503},"obj":"8757300"},{"id":"T13","span":{"begin":1056,"end":1058},"obj":"10371511"},{"id":"T14","span":{"begin":1839,"end":1841},"obj":"10371511"},{"id":"T15","span":{"begin":964,"end":965},"obj":"7700380"},{"id":"T16","span":{"begin":966,"end":967},"obj":"8885863"},{"id":"T17","span":{"begin":416,"end":417},"obj":"8610135"},{"id":"T1","span":{"begin":2289,"end":2291},"obj":"9834074"},{"id":"T2","span":{"begin":2292,"end":2294},"obj":"9536122"},{"id":"T3","span":{"begin":2280,"end":2282},"obj":"3805716"},{"id":"T4","span":{"begin":2283,"end":2285},"obj":"3140821"},{"id":"T18","span":{"begin":840,"end":841},"obj":"2423876"},{"id":"T19","span":{"begin":842,"end":843},"obj":"2352943"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/docs/sourcedb/PubMed/sourceid/"}],"text":"Introduction\nSeveral reports on the immunostimulatory properties of bacterial DNA have recently been published. Bacterial DNA directly activates B cells, monocytes, macrophages, and dendritic cells in vitro to upregulate their expression of costimulatory molecules that drive immune responses and secrete a variety of cytokines, including high levels of interleukin (IL)-12, IL-1, and tumor necrosis factor (TNF)-α [1,2,3]. Bacterial DNA indirectly activates natural killer (NK) cells and T cells [1,4,5], whereas vertebrate DNA lacks immunostimulatory effects. Unmethylated CpG motifs are common in bacterial DNA and considerably less common in vertebrate DNA [6,7]. In addition, whereas CpG motifs in bacterial DNA are unmethylated, the great majority of C and G nucleotides are methylated in all eukaryotic organisms, including mammals [6,7]. Unmethylated CpG oligodinucleotides (CpG ODNs) are responsible for the immunostimulatory properties of bacterial DNA [8,9].\nOur group has recently reported that intra-articular bacterial DNA induces arthritis [10]. Histopathological signs of the arthritis were evident within two hours and lasted for at least three weeks, and it was characterized by an influx of monocytic, Mac-1+ cells and a scarcity of T lymphocytes. Unmethylated CpG motifs were responsible for the induction of this arthritis. This proinflammatory effect of bacterial DNA did not appear to be caused by contamination with endotoxins, since mice that did not respond to lipopolysaccharides developed arthritis in response to CpG ODNs but not in response to non-DNA bacterial contamination. Neither T cells, B cells, NK cells, nor neutrophils were found to be mandatory for induction of CpG ODN-mediated arthritis, whereas macrophages played a major role in induction of arthritis triggered by CpG motifs in bacterial DNA [10].\nCytokines have been shown to exert an important role in the pathogenesis of arthritis in several mouse models. TNF-α, IL-1β, IFN-γ, and IL-12 are all produced in various quantities in the joints of patients with rheumatoid arthritis and in experimental arthritides such as collagen-induced [11,12,13,14] and septic [15] arthritis. These cytokines play an important role in the induction and development of aseptic and septic arthritis [16,17,18,19,20]. To better understand the pathogenesis of CpG ODN-mediated arthritis, we wanted to know more about the expression and role of these cytokines during its early phase. We therefore investigated the patterns of local cytokine mRNA using hybridization in situ and assessed the role of IL-12 in the induction of CpG ODN-mediated arthritis."}