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Y Dondelinger M A Aguileta V Goossens C Dubuisson S Grootjans E Dejardin P Vandenabeele M J M Bertrand 《Cell death and differentiation》2013,20(10):1381-1392
Receptor-interacting protein kinase (RIPK) 1 and RIPK3 have emerged as essential kinases mediating a regulated form of necrosis, known as necroptosis, that can be induced by tumor necrosis factor (TNF) signaling. As a consequence, inhibiting RIPK1 kinase activity and repressing RIPK3 expression levels have become commonly used approaches to estimate the contribution of necroptosis to specific phenotypes. Here, we report that RIPK1 kinase activity and RIPK3 also contribute to TNF-induced apoptosis in conditions of cellular inhibitor of apoptosis 1 and 2 (cIAP1/2) depletion or TGF-β-activated kinase 1 (TAK1) kinase inhibition, implying that inhibition of RIPK1 kinase activity or depletion of RIPK3 under cell death conditions is not always a prerequisite to conclude on the involvement of necroptosis. Moreover, we found that, contrary to cIAP1/2 depletion, TAK1 kinase inhibition induces assembly of the cytosolic RIPK1/Fas-associated protein with death domain/caspase-8 apoptotic TNF receptor 1 (TNFR1) complex IIb without affecting the RIPK1 ubiquitylation status at the level of TNFR1 complex I. These results indicate that the recruitment of TAK1 to the ubiquitin (Ub) chains, and not the Ub chains per se, regulates the contribution of RIPK1 to the apoptotic death trigger. In line with this, we found that cylindromatosis repression only provided protection to TNF-mediated RIPK1-dependent apoptosis in condition of reduced RIPK1 ubiquitylation obtained by cIAP1/2 depletion but not upon TAK1 kinase inhibition, again arguing for a role of TAK1 in preventing RIPK1-dependent apoptosis downstream of RIPK1 ubiquitylation. Importantly, we found that this function of TAK1 was independent of its known role in canonical nuclear factor-κB (NF-κB) activation. Our study therefore reports a new function of TAK1 in regulating an early NF-κB-independent cell death checkpoint in the TNFR1 apoptotic pathway. In both TNF-induced RIPK1 kinase-dependent apoptotic models, we found that RIPK3 contributes to full caspase-8 activation independently of its kinase activity or intact RHIM domain. In contrast, RIPK3 participates in caspase-8 activation by acting downstream of the cytosolic death complex assembly, possibly via reactive oxygen species generation. 相似文献
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Oliver Gordon Caetano Reis e Sousa 《BioEssays : news and reviews in molecular, cellular and developmental biology》2019,41(7)
This article reviews and discusses emerging evidence suggesting an evolutionarily‐conserved connection between injury‐associated exposure of cytoskeletal proteins and the induction of tolerance to infection, repair of tissue damage and restoration of homeostasis. While differences exist between vertebrates and invertebrates with respect to the receptor(s), cell types, and effector mechanisms involved, the response to exposed cytoskeletal proteins appears to be protective and to rely on a conserved signaling cassette involving Src family kinases, the nonreceptor tyrosine kinase Syk, and tyrosine phosphatases. A case is made for research programs that integrate different model organisms in order to increase the understanding of this putative response to tissue damage. 相似文献
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Midori Okamura Keigyou Yoh Masami Ojima Naoki Morito Satoru Takahashi 《Experimental Animals》2014,63(2):133-140
Ulcerative colitis (UC) is an inflammatory bowel disease, and its pathogenesis includes
genetic, environmental, and immunological factors, such as T helper cells and their
secreted cytokines. T helper cells are classified as Th1, Th2, and Th17 cells. However, it
is unclear which T helper cells are important in UC. Dextran sulfate sodium (DSS)-induced
colitis is a commonly used model of UC. In this study, we induced DSS colitis in Th1
dominant (T-bet transgenic (Tg)) mice, Th2 dominant (GATA-3 Tg) mice, and Th17 dominant
(RORγt Tg) mice to elucidate the roles of T helper cell in DSS colitis. The results showed
that GATA-3 Tg mice developed the most severe DSS colitis compared with the other groups.
GATA-3 Tg mice showed a significant decreased in weight from day 1 to day 7, and an
increased high score for the disease activity index compared with the other groups.
Furthermore, GATA-3 Tg mice developed many ulcers in the colon, and many neutrophils and
macrophages were detected on day 4 after DSS treatment. Measurement of GATA-3-induced
cytokines demonstrated that IL-13 was highly expressed in the colon from DSS-induced
GATA-3 Tg mice. In conclusion, GATA-3 overexpression in T-cells and IL-13 might play
important roles in the development of DSS colitis. 相似文献
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Nanako Takeda-Hirokawa Lian-pin Neoh Hiroaki Akimoto Hiroshi Kaneko Takashi Hishikawa Iwao Sekigawa Hiroshi Hashimoto Shun-ichi Hirose Tsutomu Murakami Naoki Yamamoto Tohru Mimura Yutaro Kaneko 《Microbiology and immunology》1997,41(9):741-745
To clarify the mechanism by which curdlan sulfate (CRDS) inhibits human immunodeficiency virus (HIV)-1 infection, we examined its influence on the binding of gp120 to CD4 molecules on T cells and macrophages, as well as on the production of TNF-α by gp120-stimulated macrophages (which promotes HIV-1 replication). CRDS treatment of cells not only inhibited the binding of HIV-1 gp120 to CD4+ cells, but also inhibited TNF-α production induced by gp120. Inhibition of HIV-1 infection by CRDS may be related to these two actions. 相似文献
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Min Kyoung Cho Mi Kyung Park Shin Ae Kang Seon Hee Choi Soon Cheol Ahn Hak Sun Yu 《The Korean journal of parasitology》2012,50(4):385-390
In order to know the effect of pre-existing Trichinella spiralis infection on experimentally induced intestinal inflammation and immune responses, we induced colitis in T. spiralis-infected mice and observed the severity of colitis and the levels of Th1, Th2, and regulatory cytokines and recruitment of CD4+CD25+Foxp3+ T (regulatory T; Treg) cells. Female C57BL/6 mice were infected with 250 muscle larvae; after 4 weeks, induction of experimental colitis was performed using 3% dextran sulfate sodium (DSS). During the induction period, we observed severity of colitis, including weight loss and status of stool, and evaluated the disease activity index (DAI). A significantly low DAI and degree of weight loss were observed in infected mice, compared with uninfected mice. In addition, colon length in infected mice was not contracted, compared with uninfected mice. We also observed a significant increase in production of pro-inflammatory cytokines, IL-6 and IFN-γ, in spleen lymphocytes treated with DSS; however, such an increase was not observed in infected mice treated with DSS. Of particular interest, production of regulatory cytokines, IL-10 and transforming growth factor (TGF)-β, in spleen lymphocytes showed a significant increase in mice infected with T. spiralis. A similar result was observed in mesenteric lymph nodes (MLN). Subsets of the population of Treg cells in MLN and spleen showed significant increases in mice infected with T. spiralis. In conclusion, T. spiralis infection can inhibit the DSS-induced colitis in mice by enhancing the regulatory cytokine and Treg cells recruitment. 相似文献
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Ping Li Hamish Allen Subhashis Banerjee Tara Seshadri 《Journal of cellular biochemistry》1997,64(1):27-32
Interleukin-1β converting enzyme (ICE) processes the inactive proIL-1β to the proinflammatory mature IL-1β. ICE belongs to a family of cysteine proteases that have been implicated in apoptosis. To address the biological functions of ICE, we generated ICE-deficient mice through gene targeting technology. ICE-deficient mice developed normally, appeared healthy, and were fertile. Peritoneal macrophages from ICE-deficient mice underwent apoptosis normally upon ATP treatment. Thymocytes from young ICE-deficient mice also underwent apoptosis when triggered by dexamethasone, gamma irradiation, or aging. ICE-deficient mice had a major defect in the production of mature IL-1β and had impaired IL-1α production on LPS stimulation in vitro and in vivo. ICE-deficient mice were resistant to LPS-induced endotoxic shock. J. Cell. Biochem. 64:27–32. © 1997 Wiley-Liss, Inc. 相似文献
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摘要 目的:探究紫草素(SHI)调节白细胞介素(IL)-6/信号转导子和转录激活子3(STAT3)信号通路对牙髓炎大鼠牙髓组织损伤的影响及机制。方法:建立牙髓炎大鼠模型。实验分为对照组(Control组)、模型组(Model组)、SHI低、中、高剂量组(SHI-L、SHI-M、SHI-H组,0.125 mg/kg/d、0.25 mg/kg/d、0.5 mg/kg/d SHI)、SHI高剂量+STAT3激动剂Colivelin组(SHI-H+Colivelin组,0.5 mg/kg/d SHI+1 mg/kg/d Colivelin),每组18只。观察大鼠一般行为变化;酶联免疫吸附法(ELISA)检测血清IL-6、IL-1β、肿瘤坏死因子α(TNF-α)、CXC趋化因子配体10(CXCL10)、血管内皮生长因子(VEGF)水平。苏木精-伊红(HE)染色观察牙髓组织病理变化;免疫组化法检测牙髓组织IL-6表达;免疫印迹法检测IL-6/STAT3信号通路相关蛋白表达。结果:与Control组相比,Model组大鼠饮食减少,不敢咬食物,精神萎靡;牙髓组织出现坏死,牙本质细胞排列紊乱,炎性细胞浸润及纤维组织增加,根髓充血扩张;血清IL-6、IL-1β、TNF-α、CXCL10和VEGF水平,IL-6平均光密度及IL-6和JAK2蛋白水平、p-STAT3/STAT3水平显著增加(P<0.05)。与Model组相比,SHI-L、SHI-M和SHI-H组大鼠饮食较正常,精神状态较佳,牙髓组织病理变化减轻;血清IL-6、IL-1β、TNF-α、CXCL10和VEGF水平,IL-6平均光密度及IL-6和JAK2蛋白水平、p-STAT3/STAT3水平逐渐降低(P<0.05)。与SHI-H组相比,SHI-H+Colivelin组大鼠饮食较差,精神不佳,牙髓组织病变加重;血清IL-6、IL-1β、TNF-α、CXCL10和VEGF水平,IL-6平均光密度及IL-6和JAK2蛋白水平、p-STAT3/STAT3水平显著增加(P<0.05)。结论:SHI能抑制牙髓炎大鼠炎症水平,减轻牙髓组织损伤,其机制可能与抑制IL-6/STAT3信号通路有关。 相似文献
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Jianguo Wu Hongyan Cui Zhifeng Zhu Li Wang Hong Li Desheng Wang 《Microbiology and immunology》2014,58(7):409-415
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Davood Rostamzadeh Mohammad Reza Haghshenas Farhad Daryanoosh Mahdi Samadi Ahmad Hosseini Abbas Ghaderi Zahra Mojtahedi Zohreh Babaloo 《Journal of cellular physiology》2019,234(7):11986-11998
CD11c is a member of the β2-integrin family typically used to define myeloid dendritic cells (DCs). Recent reports identify CD11c-expressing CD8+ T cells as a new subset of CD8+ regulatory T cells (Treg). Evidence exists that CD11c+CD8+ T cells may exert their effector or regulatory functions under different conditions. To date, no studies have addressed the frequency of CD11c+ T cells in cancer. Limited evidence exists in terms of expression of immune-checkpoint receptors, programmed cell death protein 1 (PD-1) and T-lymphocyte-associated antigen 4 (CTLA-4), as well as forkhead box P3 (Foxp3) in mouse lymphoid organs. Here, we have assessed CD11c+CD8+ and CD11c+CD4+ T cells, Foxp3, PD-1, and CTLA-4 expressing CD4+ T cells and CD8+ T cells in different tissues from three groups of male BALB/c mice—young, mature, and those with colorectal cancer (CRC). Analysis of CD3+CD11c+ T cells in the bone marrow (BM), spleen, and lymph nodes (LN) in each group showed a higher percentage of CD3+CD11c+ T cells in the BM from all groups and in the lymphoid organs of the cancer group compared with the young and mature groups. CD4low and CD4high cell fractions in mice BM have different expression patterns for Foxp3 and CTLA-4. We have observed a higher frequency of CD8+PD-1+ T cells in the BM, spleen, and LN of CRC mice compared with normal mice. T-cell exhaustion is associated with inhibitory receptor PD-1. According to the regulatory roles of CD11c expression in CD8+ T cells, we have proposed that the elevated percentage of CD11c, Foxp3, CTLA-4, and PD-1 expressing T cells were associated with immune response dysregulation in CRC. 相似文献
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We have recently (Kawakami et al, Immunol. Lett. 1995;46: 143) demonstrated that unusual Mac-1+CD4?CD8? T cells bearing αβ antigen receptor (Mac-1+ αβ T cells) reside in a considerable proportion in murine lungs. The present study was performed to examine the dynamics of accumulation of these cells in the lungs following intravenous administration of Mycobacterium bovis BCG (BCG). Mac-1+ αβ T cells accumulated rapidly 24 hr after infection, followed by a gradual increase over the observation period of 15 days. Furthermore, the expression of Ia, ICAM-1 and FcγR II/III on their surface intensified dramatically after BCG infection. The kinetics of enhancement of Ia expression was slower than that of ICAM-1, with the maximum level attained in one day in the latter molecule but in two weeks in the former. Neutralization of endogenous IFN-γ by specific mAb completely blocked the augmented expression of Ia on Mac-1+ αβ T cells after BCG infection, but did not have any significant effect on that of ICAM-1. In contrast, in vivo administration of IFN-γ enhanced the expression of ICAM-1 as well as that of Ia. Our results indicate that accumulation of Mac-1 αβ T cells within the lung is associated with a differential change in the expression of surface antigens, and suggest that these cells may play a role in the host defense against mycobacterial infection. 相似文献
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Role of oxygen supply in α, ω‐dodecanedioic acid biosynthesis from n‐dodecane by Candida viswanathii ipe‐1: Effect of stirring speed and aeration 下载免费PDF全文
Weifeng Cao Yujue Wang Jianquan Luo Junxiang Yin Yinhua Wan 《Engineering in Life Science》2018,18(3):196-203
α, ω‐Dodecanedioic acid (DC12) usually serves as a monomer of polyamides or some special nylons. During the biosynthesis, oxygenation cascaded in conversion of hydrophobic n‐dodecane to DC12, while the oxidation of n‐dodecane took place in the intracellular space. Therefore, it was important to investigate the role of oxygen supply on the cell growth and DC12 biosynthesis. It was found that stirring speed and aeration influenced the dissolved oxygen (DO) concentration which in turn affected cell growth as well as DC12 biosynthesis. However, the effect of culture redox potential (Orp) level on DC12 biosynthesis was more significant than that of DO level. For DC12 biosynthesis, the first step was to form the emulsion droplets through the interaction of n‐dodecane and the cell. When the stirring speed was enhanced, slits in the surface layer of the emulsion droplets would be increased. Thus, the substances transportation by water through the slits would be intensified, leading to an enhanced DC12 production. Compared with the batch culture at a lower stirring speed (400 rpm) without culture redox potential (Orp) control, the DC12 concentration was increased by 5 times up to 201.3 g/L with Orp controlled above 0 mV at a higher stirring speed (800 rpm). 相似文献
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The objective of this study is using radiolabelled PBN to determine the tissue distribution, excretion, and metabolism of PBN in rats in order to evaluate the effective time to trap free radical in appropriate tissue(s). Our results demonstrated that PBN is rapidly absorbed when it is injected intraperitoneally in the animal. PBN can be used as an effective spin trapping agent for a variety of tissues since it is evenly distributed among a wide range of tissues measured. Since there is no difference in the tissue concentrations and distribution pattern of PBN at 15, 30 and 60min after injection of PBN. it is appropriate to choose any of these time intervals to terminate the experiment and extract the spin adduct. The excretion of PBN, however, is slow. The majority of the radioactivity (70%) was excreted by the first 3 days. Only 5.7% of radioactivity was collected from 3 to 14 days. The remaining 25% of the radioactivity may be in the form of expired 14CO2. Trace amounts of radioactivity were recovered in the feces. PBN has probably only one major form of metabolite excreted in the urine. A small amount of the parent compound, however, was also excreted in the urine. The chemical structure of the metabolite(s) is still unknown. 相似文献
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Localization of α‐Dystrobrevin in Cajal Bodies and Nucleoli: A New Role for α‐Dystrobrevin in the Structure/Stability of the Nucleolus 下载免费PDF全文
Hernández‐Ibarra Jose Anselmo Laredo‐Cisneros Marco Samuel Mondragón‐González Ricardo Santamaría‐Guayasamín Natalie Cisneros Bulmaro 《Journal of cellular biochemistry》2015,116(12):2755-2765
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