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排序方式: 共有110条查询结果,搜索用时 687 毫秒
101.
Nabbe KC van Lent PL Holthuysen AE Sloëtjes AW Koch AE Radstake TR van den Berg WB 《Arthritis research & therapy》2005,7(2):R392-R401
During immune-complex-mediated arthritis (ICA), severe cartilage destruction is mediated by Fcγ receptors (FcγRs) (mainly
FcγRI), cytokines (e.g. IL-1), and enzymes (matrix metalloproteinases (MMPs)). IL-13, a T helper 2 (Th2) cytokine abundantly
found in synovial fluid of patients with rheumatoid arthritis, has been shown to reduce joint inflammation and bone destruction
during experimental arthritis. However, the effect on severe cartilage destruction has not been studied in detail. We have
now investigated the role of IL-13 in chondrocyte death and MMP-mediated cartilage damage during ICA. IL-13 was locally overexpressed
in knee joints after injection of an adenovirus encoding IL-13 (AxCAhIL-13), 1 day before the onset of arthritis; injection
of AxCANI (an empty adenoviral construct) was used as a control. IL-13 significantly increased the amount of inflammatory
cells in the synovial lining and the joint cavity, by 30% to 60% at day 3 after the onset of ICA. Despite the enhanced inflammatory
response, chondrocyte death was diminished by two-thirds at days 3 and 7. The mRNA level of FcγRI, a receptor shown to be
crucial in the induction of chondrocyte death, was significantly down-regulated in synovium. Furthermore, MMP-mediated cartilage
damage, measured as neoepitope (VDIPEN) expression using immunolocalization, was halved. In contrast, mRNA levels of MMP-3,
-9, -12, and -13 were significantly higher and IL-1 protein, which induces production of latent MMPs, was increased fivefold
by IL-13. This study demonstrates that IL-13 overexpression during ICA diminished both chondrocyte death and MMP-mediated
VDIPEN expression, even though joint inflammation was enhanced. 相似文献
102.
Paleolog EM 《Arthritis research》2002,4(Z3):S81-S90
The expansion of the synovial lining of joints in rheumatoid arthritis (RA) and the subsequent invasion by the pannus of underlying cartilage and bone necessitate an increase in the vascular supply to the synovium, to cope with the increased requirement for oxygen and nutrients. The formation of new blood vessels - termed 'angiogenesis' - is now recognised as a key event in the formation and maintenance of the pannus in RA. This pannus is highly vascularised, suggesting that targeting blood vessels in RA may be an effective future therapeutic strategy. Disruption of the formation of new blood vessels would not only prevent delivery of nutrients to the inflammatory site, but could also lead to vessel regression and possibly reversal of disease. Although many proangiogenic factors are expressed in the synovium in RA, the potent proangiogenic cytokine vascular endothelial growth factor (VEGF) has been shown to a have a central involvement in the angiogenic process in RA. The additional activity of VEGF as a vascular permeability factor may also increase oedema and hence joint swelling in RA. Several studies have shown that targeting angiogenesis in animal models of arthritis ameliorates disease. Our own study showed that inhibition of VEGF activity in murine collagen-induced arthritis, using a soluble VEGF receptor, reduced disease severity, paw swelling, and joint destruction. Although no clinical trials of anti-angiogenic therapy in RA have been reported to date, the blockade of angiogenesis - and especially of VEGF - appears to be a promising avenue for the future treatment of RA. 相似文献
103.
Advanced glycation end products upregulate angiogenic and pro-inflammatory cytokine production in human monocyte/macrophages 总被引:5,自引:0,他引:5
Pertyńska-Marczewska M Kiriakidis S Wait R Beech J Feldmann M Paleolog EM 《Cytokine》2004,28(1):35-47
Glucose can react non-enzymatically with amino groups of, for example, proteins, to yield derivatives termed advanced glycation end products (AGE), which contribute to many chronic progressive diseases associated with microvascular complications. The study aimed to determine the effect of AGE-modified albumin on THP-1 cells and human monocyte-derived macrophages. Bovine serum albumin (BSA) or human serum albumin (HSA), modified by glucose-derived AGE, was prepared by incubation with glucose for differing periods of time. Alternatively, BSA was incubated with sodium cyanoborohydride and glyoxylic acid to produce N(epsilon)-(carboxymethyl)lysine-modified BSA (CML-BSA). Stimulation for 24h of THP-1 cells with BSA, incubated for 6-8 weeks with glucose, induced significant VEGF release. Human monocyte-derived macrophages stimulated with extensively glycated HSA also showed significant VEGF release, as well as upregulation of IL-8 production, incubation for 6h with extensively glycated HSA increased release of TNFalpha and expression of tissue factor. Finally, addition of CML-BSA resulted in significant induction of TNFalpha and VEGF release. We demonstrate that a range of different methods of glycation of BSA and HSA, including CML-BSA, resulted in the induction of VEGF, TNFalpha, IL-8 and expression of tissue factor, according to length of stimulation and different glycation products used, suggesting that AGE-induced activation of macrophages may contribute to vascular complications by regulation of angiogenic, inflammatory and pro-coagulant processes. 相似文献
104.
Djie Tjwan Thung Joep de Ligt Lisenka EM Vissers Marloes Steehouwer Mark Kroon Petra de Vries Eline P Slagboom Kai Ye Joris A Veltman Jayne Y Hehir-Kwa 《Genome biology》2014,15(10)
Mobile elements are major drivers in changing genomic architecture and can cause disease. The detection of mobile elements is hindered due to the low mappability of their highly repetitive sequences. We have developed an algorithm, called Mobster, to detect non-reference mobile element insertions in next generation sequencing data from both whole genome and whole exome studies. Mobster uses discordant read pairs and clipped reads in combination with consensus sequences of known active mobile elements. Mobster has a low false discovery rate and high recall rate for both L1 and Alu elements. Mobster is available at http://sourceforge.net/projects/mobster.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0488-x) contains supplementary material, which is available to authorized users. 相似文献105.
106.
K van Oers A W Santure I De Cauwer N EM van Bers R PMA Crooijmans B C Sheldon M E Visser J Slate M AM Groenen 《Heredity》2014,112(3):307-316
Linking variation in quantitative traits to variation in the genome is an important, but
challenging task in the study of life-history evolution. Linkage maps provide a valuable
tool for the unravelling of such trait−gene associations. Moreover, they give
insight into recombination landscapes and between-species karyotype evolution. Here we
used genotype data, generated from a 10k single-nucleotide polymorphism (SNP) chip, of
over 2000 individuals to produce high-density linkage maps of the great tit (Parus
major), a passerine bird that serves as a model species for ecological and
evolutionary questions. We created independent maps from two distinct populations: a
captive F2-cross from The Netherlands (NL) and a wild population from the United Kingdom
(UK). The two maps contained 6554 SNPs in 32 linkage groups, spanning 2010 cM and
1917 cM for the NL and UK populations, respectively, and were similar in size and
marker order. Subtle levels of heterochiasmy within and between chromosomes were
remarkably consistent between the populations, suggesting that the local departures from
sex-equal recombination rates have evolved. This key and surprising result would have been
impossible to detect if only one population was mapped. A comparison with zebra finch
Taeniopygia guttata, chicken Gallus gallus and the green anole lizard
Anolis carolinensis genomes provided further insight into the evolution of
avian karyotypes. 相似文献
107.
108.
109.
110.
Marieke Biegstraaten Ivo N van Schaik Wouter Wieling Frits A Wijburg Carla EM Hollak 《BMC neurology》2010,10(1):38