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51.
Constantin N. Baxevanis Angelos D. Gritzapis George V. Z. Dedoussis Nikolaos G. Papadopoulos Orestes Tsolas Michael Papamichail 《Cancer immunology, immunotherapy : CII》1994,38(4):281-286
We have recently demonstrated that prothymosin (ProT) when administered intraperitoneally (i.p.) protects DBA/2 mice against the growth of syngeneic leukemic L1210 cells through the induction of tumoricidal peritoneal cells producing high levels of tumor necrosis factor (TNF) [Papanastasiou et al. (1992) Cancer Immunol Immunother 35: 145]. In this report we tested further immunological alterations that may be caused by the administration of ProT in vivo. We demonstrate that i.p. injections of ProT enhance natural killer (NK) cell activity and induce lymphokine-activated (LAK) activity in vivo. Thus, splenocytes from ProT-treated DBA/2 animals exhibited significantly higher cytotoxic activity (up to threefold) against the NK-sensitive YAC cell line and the NK-resistant P815 and L1210 syngeneic tumor cells, as compared to splenocytes from syngeneic control mice. The enhancement of the cytotoxic profile of DBA/2 splenocytes was associated with increased percentages of CD8+ cells, NK cells and activated CD3+ cells. The ProT-induced effect persisted for 30 days after the end of the ProT treatment period and returned to normal levels 20 days later. SPlenocytes from non-treated DBA/2 animals generated high NK and LAK activities in response to ProT in vitro. The ProT-induced NK an LAK activities reached 84% and 75% respectively of what was obtained with interleukin-2 (IL-2). High concentrations of TNF and IL-2 were generated in response to ProT in LAK cultures. These findings suggest that ProT may provide an overall protective effect against tumor growth in vivo through induction of NK and LAK activities possibly indirectly via the production of IL-2 and TNF in the spleen, peritoneal cavity and probably other lymphoid organs.This work was supported by a CEC grant to M. Papamichail 相似文献
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53.
Seigo Terawaki Voahirana Camosseto Francesca Prete Till Wenger Alexia Papadopoulos Christiane Rondeau Alexis Combes Christian Rodriguez Rodrigues Thien-Phong Vu Manh Mathieu Fallet Luc English Rodrigo Santamaria Ana R. Soares Tobias Weil Hamida Hammad Michel Desjardins Jean-Pierre Gorvel Manuel A.S. Santos Evelina Gatti Philippe Pierre 《The Journal of cell biology》2015,210(7):1133-1152
Autophagy is a key degradative pathway coordinated by external cues, including starvation, oxidative stress, or pathogen detection. Rare are the molecules known to contribute mechanistically to the regulation of autophagy and expressed specifically in particular environmental contexts or in distinct cell types. Here, we unravel the role of RUN and FYVE domain–containing protein 4 (RUFY4) as a positive molecular regulator of macroautophagy in primary dendritic cells (DCs). We show that exposure to interleukin-4 (IL-4) during DC differentiation enhances autophagy flux through mTORC1 regulation and RUFY4 induction, which in turn actively promote LC3 degradation, Syntaxin 17–positive autophagosome formation, and lysosome tethering. Enhanced autophagy boosts endogenous antigen presentation by MHC II and allows host control of Brucella abortus replication in IL-4–treated DCs and in RUFY4-expressing cells. RUFY4 is therefore the first molecule characterized to date that promotes autophagy and influences endosome dynamics in a subset of immune cells. 相似文献
54.
Donald Beqollari Christin F. Romberg Dilyana Filipova Ulises Meza Symeon Papadopoulos Roger A. Bannister 《The Journal of general physiology》2015,146(1):97-108
In skeletal muscle, excitation–contraction (EC) coupling requires depolarization-induced conformational rearrangements in L-type Ca2+ channel (CaV1.1) to be communicated to the type 1 ryanodine-sensitive Ca2+ release channel (RYR1) of the sarcoplasmic reticulum (SR) via transient protein–protein interactions. Although the molecular mechanism that underlies conformational coupling between CaV1.1 and RYR1 has been investigated intensely for more than 25 years, the question of whether such signaling occurs via a direct interaction between the principal, voltage-sensing α1S subunit of CaV1.1 and RYR1 or through an intermediary protein persists. A substantial body of evidence supports the idea that the auxiliary β1a subunit of CaV1.1 is a conduit for this intermolecular communication. However, a direct role for β1a has been difficult to test because β1a serves two other functions that are prerequisite for conformational coupling between CaV1.1 and RYR1. Specifically, β1a promotes efficient membrane expression of CaV1.1 and facilitates the tetradic ultrastructural arrangement of CaV1.1 channels within plasma membrane–SR junctions. In this paper, we demonstrate that overexpression of the RGK protein Rem, an established β subunit–interacting protein, in adult mouse flexor digitorum brevis fibers markedly reduces voltage-induced myoplasmic Ca2+ transients without greatly affecting CaV1.1 targeting, intramembrane gating charge movement, or releasable SR Ca2+ store content. In contrast, a β1a-binding–deficient Rem triple mutant (R200A/L227A/H229A) has little effect on myoplasmic Ca2+ release in response to membrane depolarization. Thus, Rem effectively uncouples the voltage sensors of CaV1.1 from RYR1-mediated SR Ca2+ release via its ability to interact with β1a. Our findings reveal Rem-expressing adult muscle as an experimental system that may prove useful in the definition of the precise role of the β1a subunit in skeletal-type EC coupling. 相似文献
55.
Pavlik R Wypior G Hecht S Papadopoulos P Kupka M Thaler C Wiest I Pestka A Friese K Jeschke U 《Histochemistry and cell biology》2011,136(3):289-299
Estradiol and progesterone mediate their actions by binding to classical nuclear receptors, estrogen receptor α (ERα) and
estrogen receptor β (ERβ) and progesterone receptor A and B (PR-A and PR-B) and the non-classical G protein-coupled estrogen
receptor (GPER). Several animal knock-out models have shown the importance of the receptors for growth of the oocyte and ovulation.
The aim of our study was to identify GPER in human granulosa cells (GC) for the first time. Moreover, the effect of different
doses of gonadotropins on estrogen and progesterone receptors in the human ovary should be investigated as follicle stimulating
hormone (FSH) and luteinizing hormone (LH) are also responsible for numerous mechanisms in the ovary like induction of the
steroid biosynthesis. Human GC were cultured in vitro and stimulated with different doses of recombinant human FSH or LH.
Receptor expression was analyzed by immunocytochemistry and quantitative real-time RT-PCR. GPER could be identified for the
first time in human GC. It could be shown that high concentrations of LH increase GPER protein expression. Furthermore FSH
and LH increased ERβ, PR-A and PR-B significantly on protein level. These findings were verified for high doses of FSH and
LH on mRNA level. ERα was not affected with FSH or LH. We assume that gonadotropins induce GPER, ERβ and PR in luteinized
granulosa cells. 相似文献
56.
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58.
Luminita A Stanciu Kevan Roberts Nikolaos G Papadopoulos Sang-Heon Cho Stephen T Holgate Anthony J Coyle Sebastian L Johnston 《Respiratory research》2005,6(1):67
Background
Virus infections are the major cause of asthma exacerbations. CD8+ T cells have an important role in antiviral immune responses and animal studies suggest a role for CD8+ T cells in the pathogenesis of virus-induced asthma exacerbations. We have previously shown that the presence of IL-4 during stimulation increases the frequency of IL-5-positive cells and CD30 surface staining in CD8+ T cells from healthy, normal subjects. In this study, we investigated whether excess IL-4 during repeated TCR/CD3 stimulation of CD8+ T cells from atopic asthmatic subjects alters the balance of type 1/type 2 cytokine production in favour of the latter.Methods
Peripheral blood CD8+ T cells from mild atopic asthmatic subjects were stimulated in vitro with anti-CD3 and IL-2 ± excess IL-4 and the expression of activation and adhesion molecules and type 1 and type 2 cytokine production were assessed.Results
Surface expression of very late antigen-4 [VLA-4] and LFA-1 was decreased and the production of the type 2 cytokines IL-5 and IL-13 was augmented by the presence of IL-4 during stimulation of CD8+ T cells from mild atopic asthmatics.Conclusion
These data suggest that during a respiratory virus infection activated CD8+ T cells from asthmatic subjects may produce excess type 2 cytokines and may contribute to asthma exacerbation by augmenting allergic inflammation. 相似文献59.
Apostolos Bossios Stelios Psarras Dimitrios Gourgiotis Chrysanthi L Skevaki Andreas G Constantopoulos Photini Saxoni-Papageorgiou Nikolaos G Papadopoulos 《Respiratory research》2005,6(1):114
Background
Human rhinoviruses (RV), the most common triggers of acute asthma exacerbations, are considered not cytotoxic to the bronchial epithelium. Recent observations, however, have questioned this knowledge. The aim of this study was to evaluate the ability of RV to induce epithelial cytotoxicity and affect epithelial repair in-vitro.Methods
Monolayers of BEAS-2B bronchial epithelial cells, seeded at different densities were exposed to RV serotypes 1b, 5, 7, 9, 14, 16. Cytotoxicity was assessed chromatometrically. Epithelial monolayers were mechanically wounded, exposed or not to RV and the repopulation of the damaged area was assessed by image analysis. Finally epithelial cell proliferation was assessed by quantitation of proliferating cell nuclear antigen (PCNA) by flow cytometry.Results
RV1b, RV5, RV7, RV14 and RV16 were able to induce considerable epithelial cytotoxicity, more pronounced in less dense cultures, in a cell-density and dose-dependent manner. RV9 was not cytotoxic. Furthermore, RV infection diminished the self-repair capacity of bronchial epithelial cells and reduced cell proliferation.Conclusion
RV-induced epithelial cytotoxicity may become considerable in already compromised epithelium, such as in the case of asthma. The RV-induced impairment on epithelial proliferation and self-repair capacity may contribute to the development of airway remodeling. 相似文献60.
Papadopoulos S Leuranguer V Bannister RA Beam KG 《The Journal of biological chemistry》2004,279(42):44046-44056
Excitation-contraction coupling in skeletal muscle involves conformational coupling between the dihydropyridine receptor (DHPR) and the type 1 ryanodine receptor (RyR1) at junctions between the plasma membrane and sarcoplasmic reticulum. In an attempt to find which regions of these proteins are in close proximity to one another, we have constructed a tandem of cyan and yellow fluorescent proteins (CFP and YFP, respectively) linked by a 23-residue spacer, and measured the fluorescence resonance energy transfer (FRET) of the tandem either in free solution or after attachment to sites of the alpha1S and beta1a subunits of the DHPR. For all of the sites examined, attachment of the CFP-YFP tandem did not impair function of the DHPR as a Ca2+ channel or voltage sensor for excitation-contraction coupling. The free tandem displayed a 27.5% FRET efficiency, which decreased significantly after attachment to the DHPR subunits. At several sites examined for both alpha1S (N-terminal, proximal II-III loop of a two fragment construct) and beta1a (C-terminal), the FRET efficiency was similar after expression in either dysgenic (alpha1S-null) or dyspedic (RyR1-null) myotubes. However, compared with dysgenic myotubes, the FRET efficiency in dyspedic myotubes increased from 9.9 to 16.7% for CFP-YFP attached to the N-terminal of beta1a, and from 9.5 to 16.8% for CFP-YFP at the C-terminal of alpha1S. Thus, the tandem reporter suggests that the C terminus of alpha1S and the N terminus of beta1a may be in close proximity to the ryanodine receptor. 相似文献