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51.
Dimerization of the major birch pollen allergen Bet v 1 is important for its in vivo IgE-cross-linking potential in mice 总被引:1,自引:0,他引:1
Schöll I Kalkura N Shedziankova Y Bergmann A Verdino P Knittelfelder R Kopp T Hantusch B Betzel C Dierks K Scheiner O Boltz-Nitulescu G Keller W Jensen-Jarolim E 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(10):6645-6650
In type I allergy, the cross-linking of membrane IgE on B lymphocytes and of cytophilic IgE on effector cells by their respective allergens are key events. For cross-linking two IgE molecules, allergens need at least two epitopes. On large molecules, these could be different epitopes in a multivalent, or identical epitopes in a symmetrical, fashion. However, the availability of epitopes may be limited on small allergens such as Bet v 1, the major birch pollen allergen. The present work analyzes whether dimerization is required for the cross-linking capacity of this allergen. In immunoblots, murine monoclonal and polyclonal human Bet v 1-specific Abs detected, besides a Bet v 1 monomer of 17 kDa, a dimer of 34 kDa. In dynamic light scattering, Bet v 1 appeared as dimers and even multimers, but a single condition could be defined where it behaved exclusively monomerically. Small-angle x-ray scattering of the monomeric and dimeric samples resulted in diagrams agreeing with the calculated models. Circular dichroism measurements indicated that the structure of Bet v 1 was preserved under monomeric conditions. Skin tests in Bet v 1-allergic mice were positive with Bet v 1 dimer, but remained negative using the monomer. Furthermore, in contrast to dimeric Bet v 1, the monomer was less capable of activating murine memory B cells for IgE production in vivo. Our data indicate that the presentation of two identical epitopes by dimerized allergens is a precondition for cross-linking of IgE on mast cells and B lymphocytes. 相似文献
52.
Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent proteolytic enzymes, which degrade several components of extracellular matrix, in arthritic synovial cells. In cultured synovial fibroblasts, both nitric oxide (NO) and reactive oxygen species (ROS) are potent inducers of MMPs production. PEP1261, a tetrapeptide derivative used in this study, corresponds to residues of 39-42 human lactoferrin. The parent protein lactoferrin is able to inhibit the production of free radicals in rheumatoid joints and it regulates many aspects of inflammation. This study is aimed to examine the effects of PEP1261 on MMP-2 production in the presence of nitric oxide donor in cultured synovial fibroblasts from collagen-induced arthritic rats. PEP1261 affects a significant reduction in nitrite levels as well as in MMP-2 production in SNAP stimulated synovial fibroblasts and this is validated by gelatin zymography and immunoblot analysis. Furthermore, RTPCR analysis has demonstrated that PEP1261 inhibits MMP-2 mRNA expression in SNAP treated synovial fibroblasts. The results of this study suggest that PEP1261 possesses antiarthritic activity by inhibiting nitrite levels as well as MMP-2 expression better than control peptides viz., KRDS and RGDS. 相似文献
53.
Xia Y Yeddula N Leblanc M Ke E Zhang Y Oldfield E Shaw RJ Verma IM 《Nature cell biology》2012,14(3):257-265
Lung cancer is one of the leading cancer malignancies, with a five-year survival rate of only ~15%. We have developed a lentiviral-vector-mediated mouse model, which enables generation of non-small-cell lung cancer from less than 100 alveolar epithelial cells, and investigated the role of IKK2 and NF-κB in lung-cancer development. IKK2 depletion in tumour cells significantly attenuated tumour proliferation and significantly prolonged mouse survival. We identified Timp1, one of the NF-κB target genes, as a key mediator for tumour growth. Activation of the Erk signalling pathway and cell proliferation requires Timp-1 and its receptor CD63. Knockdown of either Ikbkb or Timp1 by short hairpin RNAs reduced tumour growth in both xenograft and lentiviral models. Our results thus suggest the possible application of IKK2 and Timp-1 inhibitors in treating lung cancer. 相似文献
54.
Vijayalakshmi A Tarunashree Y Baruwati B Manorama SV Narayana BL Johnson RE Rao NM 《Biosensors & bioelectronics》2008,23(11):1708-1714
Ion-selective field effect transistor (ISFET) is a robust platform to develop biosensors. A variety of methods are used including covalent attachment or polymer entrapment, to associate enzymes or antibodies to the gate surface of a FET. We have employed a novel method of retaining the enzyme molecules at the gate surface by immobilizing the enzyme on magnetic nickelferrite nanoparticles and applying a permanent magnet below the gate of the FET. We were able to estimate the triglyceride concentrations in the range of 0.1–1.5% by immobilizing a thermostable lipase on nanoparticles. Tributyrin, trioctanoate and triolein have given similar results. The reaction volume could be scaled down to 0.2 ml without a loss in slope or sensitivity. Ionic strength (>150 mM NaCl) has a strong influence on the sensitivity of the measurement. The advantages of this configuration of enzyme biosensor are reduction of mass transfer problems, increasing the amount of enzyme at the gate surface besides providing an opportunity to use a single FET device for multiple analyte detection. 相似文献
55.
Manda Sathish Sabanis Chetan Dushantrao Shalini Nekkanti Ramya Tokala Soujanya Thatikonda Yellaiah Tangella Gunda Srinivas Shirisha Cherukommu Namballa Hari Krishna Nagula Shankaraiah Narayana Nagesh Ahmed Kamal 《Bioorganic & medicinal chemistry》2018,26(17):4916-4929
A series of new C3-trans-cinnamide linked β-carboline conjugates has been synthesized by coupling between various β-carboline amines and substituted cinnamic acids. Evaluation of their anti-proliferative activity against a panel of selected human cancer cell lines such as A549 (lung cancer), MCF-7 (breast cancer), B16 (melanoma), HeLa (cervical cancer) and a normal cell line NIH3T3 (mouse embryonic fibroblast cell line), suggested that the newly designed conjugates are considerably active against all the tested cancer cell lines with IC50 values 13–45?nM. Moreover, the conjugates 8v and 8x were the most active against MCF-7 cells (14.05?nM and 13.84?nM respectively) and also even potent on other cell lines tested. Further, detailed investigations such as cell cycle analysis, apoptosis induction study, topoisomerase I inhibition assay, DNA binding affinity and docking studies revealed that these new conjugates are DNA interactive topoisomerase I inhibitors. 相似文献
56.
The effects of the trichothecene mycotoxins (acetyl T-2 toxin, T-2 toxin, HT-2 toxin, palmityl T-2 toxin, diacetoxyscirpenol (DAS), deoxynivalenol (DON), and T-2 tetraol) on bovine platelet function were examined in homologous plasma stimulated with platelet activating factor (PAF). The mycotoxins inhibited platelet function with the following order of potency: acetyl T-2 toxin > palmityl T-2 toxin = DAS > HT-2 toxin = T-2 toxin. While T-2 tetraol was completely ineffective as an inhibitor, DON exhibited minimal inhibitory activity at concentrations above 10×10?4M. The stability of the platelet aggregates formed was significantly reduced in all mycotoxin treated platelets compared to that of the untreated PAF controls. It is suggested that the increased sensitivity of PAF stimulated bovine platelets to the more lipophilic mycotoxins may be related to their more efficient partitioning into the platelet membrane compared to the more hydrophilic compounds. 相似文献
57.
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59.
Stationary-phase mutagenesis in nondividingE. coli cells exposed to a nonlethal stress was, a few years ago, claimed to be a likely case of a Lamarckian mechanism capable of
producing exclusively useful mutations in a directed manner. After a heated debate over the last decade it now appears to
involve a Darwinian mechanism that generates a transient state of hypermutagenesis, operating on a large number of sites spread
over the entire genome, at least in a proportion of the resting cells. Most of the studies that clarified this position were
on the reversion of a frameshift mutation present in alacI-lacZ fusion inE. coli strain FC40. Several groups have extensively examined both the sequence changes associated with these reversions and the
underlying genetic requirements. On the basis of our studies on the genomic sequence analysis, we recently proposed a model
to explain the specific changes associated with the reversion hotspots. Here we propose a more detailed version of this model
that also takes into account the observed genetic requirements of stationary-state mutagenesis. Briefly, G:T/U mismatches
produced at methylatable cytosines are preferentially repaired in nondividing cells by the very short patch mismatch repair
(VSPMR) mechanism which is itself mutagenic and can produce mutations in very short stretches located in the immediate vicinity
of these cytosine methylation sites. This mechanism requires a homologous or homeologous strand invasion step and an error-prone
DNA synthesis step and is dependent on RecA, RecBCD and a DNA polymerase. The process is initiated near sequences recognized
by Dcm and Vsr enzymes and further stimulated if these sequences are a part of CHI or CHI-like sequences, but a double-strand-break-dependent
recombination mediated by the RecBCD pathways proposed by others seems to be nonessential. The strand transfer step is proposed
to depend on RecA, RuvA, RuvB and RuvC and is opposed by RecG and MutS. The model also gives interesting insights into the
evolution of theE. coli genome. 相似文献
60.
Elisabeth APM Romme Piet Geusens Willem F Lems Erica PA Rutten Frank WJM Smeenk Joop PW van den Bergh Peter ThW van Hal Emiel FM Wouters 《Respiratory research》2015,16(1)
Although osteoporosis and its related fractures are common in patients with COPD, patients at high risk of fracture are poorly identified, and consequently, undertreated. Since there are no fracture prevention guidelines available that focus on COPD patients, we developed a clinical approach to improve the identification and treatment of COPD patients at high risk of fracture. We organised a round-table discussion with 8 clinical experts in the field of COPD and fracture prevention in the Netherlands in December 2013. The clinical experts presented a review of the literature on COPD, osteoporosis and fracture prevention. Based on the Dutch fracture prevention guideline, they developed a 5-step clinical approach for fracture prevention in COPD. Thereby, they took into account both classical risk factors for fracture (low body mass index, older age, personal and family history of fracture, immobility, smoking, alcohol intake, use of glucocorticoids and increased fall risk) and COPD-specific risk factors for fracture (severe airflow obstruction, pulmonary exacerbations and oxygen therapy). Severe COPD (defined as postbronchodilator FEV1 < 50% predicted) was added as COPD-specific risk factor to the list of classical risk factors for fracture. The 5-step clinical approach starts with case finding using clinical risk factors, followed by risk evaluation (dual energy X-ray absorptiometry and imaging of the spine), differential diagnosis, treatment and follow-up. This systematic clinical approach, which is evidence-based and easy-to-use in daily practice by pulmonologists, should contribute to optimise fracture prevention in COPD patients at high risk of fracture. 相似文献