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51.
Frederique M Moret Kim MG van der Wurff-Jacobs Johannes WJ Bijlsma Floris PJG Lafeber Joel AG van Roon 《Arthritis research & therapy》2014,16(6)
Introduction
The aim of this study was to investigate PD-1/PD-L1 involvement in the hyporesponsiveness of rheumatoid arthritis (RA) synovial fluid (SF) CD4 T cells upon stimulation by thymic stromal lymphopoietin (TSLP)–primed CD1c myeloid dendritic cells (mDCs).Methods
Expression of PD-1 on naïve (Tn), central memory (Tcm) and effector memory (Tem) CD4 T cell subsets was assessed by flow cytometry. PD-L1 expression and its regulation upon TSLP stimulation of mDCs from peripheral blood (PB) and SF of RA patients were investigated by quantitative RT-PCR and flow cytometry. The involvement of PD-1/PD-L1 interactions in SF T cell hyporesponsiveness upon (TSLP-primed) mDC activation was determined by cell culture in the presence of PD-1 blocking antibodies, with or without interleukin 7 (IL-7) as a recognized suppressor of PD-1 expression.Results
PD-1 expression was increased on CD4 T cells derived from SF compared with PB of RA patients. TSLP increased PD-L1 mRNA expression in both PB and SF mDCs. PD-L1 protein expression was increased on SF mDCs compared with PB mDCs and was associated with T cell hyporesponsiveness. Blockade of PD-1, as well as IL-7 stimulation, during cocultures of memory T cells and (TSLP-primed) mDCs from RA patients significantly recovered T cell proliferation.Conclusion
SF T cell hyporesponsiveness upon (TSLP-primed) mDC stimulation in RA joints is partially dependent on PD-1/PD-L1 interactions, as PD-1 and PD-L1 are both highly expressed on SF T cells and mDCs, respectively, and inhibiting PD-1 availability restores T cell proliferation. The potential of IL-7 to robustly reverse this hyporesponsiveness suggests that such proinflammatory cytokines in RA joints strongly contribute to memory T cell activation. 相似文献52.
53.
54.
Complete nucleotide sequences of bovine alpha S2- and beta-casein cDNAs: comparisons with related sequences in other species 总被引:2,自引:0,他引:2
Stewart AF; Bonsing J; Beattie CW; Shah F; Willis IM; Mackinlay AG 《Molecular biology and evolution》1987,4(3):231-241
The nucleotide sequences corresponding to bovine alpha S2- and beta- casein
mRNAs have been determined by cDNA analysis. Both sequences appear to be
complete at their 5' ends. The nucleotide sequence of alpha S2-casein, when
compared with the corresponding cavine A sequence, helps to define the
boundaries of a large amino acid repeat (approximately 80 residues) whereas
comparisons with the nucleotide sequences of rat gamma- and mouse
epsilon-casein mRNAs also reveal extensive sequence similarities. An
alignment of these four sequences shows that the divergence of their
translated regions has been characterized by the duplication and deletion
of discrete segments of sequence that probably correspond to exons. A high
degree of nucleotide substitution is also found when the four sequences are
compared, except for well-conserved leader-peptide and phosphorylation-site
sequences and, to a lesser extent, the 5'-untranslated regions. Similar
comparison of the bovine and rat beta-caseins shows that their divergence
has involved a high rate of nucleotide substitution but that no major
insertions or deletions of sequence have occurred. The several splice sites
that have veen defined in the rat beta-casein gene are likely to have been
conserved in the bovine. The contrasting evolutionary histories of the
alpha- and beta-casein coding sequences correlate with the distinctive
functions of these proteins in the casein micelle system in milk.
相似文献
55.
Effect of self-association on the structural organization of partially folded proteins: inactivated actin 总被引:1,自引:0,他引:1 下载免费PDF全文
IM Kuznetsova AG Biktashev SY Khaitlina KS Vassilenko KK Turoverov VN Uversky 《Biophysical journal》1999,77(5):2788-2800
The propensity to associate or aggregate is one of the characteristic properties of many nonnative proteins. The aggregation of proteins is responsible for a number of human diseases and is a significant problem in biotechnology. Despite this, little is currently known about the effect of self-association on the structural properties and conformational stability of partially folded protein molecules. G-actin is shown to form equilibrium unfolding intermediate in the vicinity of 1.5 M guanidinium chloride (GdmCl). Refolding from the GdmCl unfolded state is terminated at the stage of formation of the same intermediate state. An analogous form, known as inactivated actin, can be obtained by heat treatment, or at moderate urea concentration, or by the release of Ca(2+). In all cases actin forms specific associates comprising partially folded protein molecules. The structural properties and conformational stability of inactivated actin were studied over a wide range of protein concentrations, and it was established that the process of self-association is rather specific. We have also shown that inactivated actin, being denatured, is characterized by a relatively rigid microenvironment of aromatic residues and exhibits a considerable limitation in the internal mobility of tryptophans. This means that specific self-association can play an important structure-forming role for the partially folded protein molecules. 相似文献
56.
Polygalacturonase (PG) activity and changes in respiratory intensity of apple fruits were investigated. The respiratory rate was decreased to a preclimacteric minimum from 30 Aug. to 20 Sept., Then increased to a climacteric peak (20–30 Sept.) and again drop down gradually with approaching the senescence stage. The PG activity was undetectable in a developing fruit until the onset climacteric phase. It rose rapidly after harvest, and reaching its highest level on 27 Oct. Just a month after the climacteric peak. The PG activity fell gradually. The amount of the fractions of pectic acid in fruits changed with the modifications of PG activity. With the ripening of fruits, the content of alcohol-soluble small molecules of pectic acids was increased from 12 to 13 5 mg/100 g of tissue, while the amount of alcohol- insoluble large molecules of pectic acids reduced from 530 to 280/100 g of tissue. PG activity would indicate the destruction of cell walls and the separation of cells. The onset of softening of fruits occurred 20 days after the rise of PG activity. It is supposed that the process of softening is directly controlled by PG activity. 相似文献
57.
C. H. Andrewes 《Microbiological reviews》1965,29(1):1-8
58.
AG. van Ginkel BJ. Sorgdrager M. A. de Graaf I. Karalis N. Ajmone Marsan 《Netherlands heart journal》2014,22(2):77-79
We report a case of an allergic reaction after the administration of an echocardiographic contrast agent which resulted in ST-segment elevation. Hypersensitivity and allergic reactions are known causes of acute cardiovascular events. However, only limited reports are available which suggest the exact mechanism of the occurrence of angina or myocardial infarction during severe allergic reactions. In our case, through invasive imaging (coronary angiography and IVUS) we have shown for the first time a transient coronary spasm in the absence of intra-coronary thrombus and only minimal neointimal hyperplasia. 相似文献
59.
Román González-Prieto Sabine AG Cuijpers Martijn S Luijsterburg Haico van Attikum Alfred CO Vertegaal 《EMBO reports》2015,16(4):512-519
SUMOylation plays important roles in the DNA damage response. However, whether it is important for interstrand crosslink repair remains unknown. We report that the SLX4 nuclease scaffold protein is regulated by SUMOylation. We have identified three SUMO interaction motifs (SIMs) in SLX4, mutating all of which abrogated the binding of SLX4 to SUMO-2 and covalent SLX4 SUMOylation. An SLX4 mutant lacking functional SIMs is not recruited to PML nuclear bodies nor stabilized at laser-induced DNA damage sites. Additionally, we elucidated a novel role for PARylation in the recruitment of SLX4 to sites of DNA damage. Combined, our results uncover how SLX4 is regulated by post-translational modifications. 相似文献
60.
Joel AG van Roon 《Arthritis research & therapy》2007,9(4):106
Fcγ receptors (FcγRs) bind the constant Fc region of IgG molecules. IgG/antigen-containing immune complexes elicit a variety
of effector functions in cells that express activating FcγRs. Because activating FcγRs are present on cells from the innate
immune system, such as dendritic cells, monocytes/macrophages and granulocytes, these IgG receptors form a crucial link between
the innate and the acquired immune systems. Recently, the ability to detect the inhibitory FcγRIIb on cells has indicated
an imbalance between activating and inhibitory FcγRs in rheumatoid arthritis. This progress offers an opportunity to study
modulation of FcγR balance and could stimulate development of FcγR-directed immunotherapy. 相似文献