共查询到20条相似文献,搜索用时 31 毫秒
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Ai Suzaki Shihoko Komine‐Aizawa Satoshi Hayakawa 《Journal of orthopaedic research》2014,32(7):910-914
Peripheral endothelin‐1 (ET‐1) levels are increased in chronic systemic disorders such as congestive cardiac failure, diabetes and chronic renal failure. Bone infections are also associated with poor prognoses in these conditions. In the present study, we examined the alterations in Toll‐like receptor 2 (TLR2) signaling induced by ET‐1 in an in vitro osteoblast cell model. The TLR2‐positive murine osteoblast cell line MC3T3‐E1 was treated with heat‐killed Listeria monocytogenes (HKLM), a TLR2 ligand, in the presence or absence of ET‐1. We examined TLR2 expression, intranuclear NF‐κB phosphorylation and interleukin 6 (IL‐6) production. ET‐1 suppressed cell surface expression of TLR2, NF‐κB phosphorylation and IL‐6 production. As TLR2 represents an important mechanism by which osteoblasts recognize bacterial pathogens, a continuously elevated ET‐1 status may impair pathogenic recognition by osteoblasts and consequently affect bone metabolism during infections. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:910–914, 2014. 相似文献
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Inken Hilgendorf Brigitte Mueller‐Hilke Günther Kundt Ernst Holler Petra Hoffmann Matthias Edinger Mathias Freund Daniel Wolff 《Transplant international》2012,25(1):87-96
The chronic graft‐versus host disease (cGVHD) is associated with a perturbed B cell homeostasis and an increased infection rate. Aiming to determine the impact of lymphocyte subsets on cGVHD, blood samples from 98 patients at least 100 days following allogeneic haematopoietic stem cell transplantation (median 1066 days) were analyzed, serum levels of immunoglobulins measured and the incidence of severe infections retrospectively documented. Absolute CD19+ B cell counts, including counts of immature (CD10+ CD38++ CD20+ IgM++) and transitional (CD10? CD38++ CD20+ IgM++) as well as class switched memory (CD19+ CD27+ IgM? IgD?) B cells in patients with active cGVHD (n = 52) were significantly decreased as compared to those with inactive (n = 18) or without cGVHD (n = 28). In addition, nonclass switched IgM+ memory B cells (CD19+ CD27+ IgM+ IgD+) were absent in patients with cGVHD, but not in patients with inactive (0.4 × 106/l) or without (1.7 × 106/l) cGVHD (both P < 0.001). In line with these results we found significantly decreased lgG levels in patients with cGVHD, which was associated with a significantly higher rate of severe infections in cGVHD patients. Our data underline the close association of diminished B cell counts with cGVHD and the onset of severe infections. The lack of IgM+ memory B cells in patients with cGVHD may indicate functional asplenia. 相似文献
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Fumiyo Ikeda Takuma Matsubara Taro Tsurukai Kenji Hata Riko Nishimura PhD Toshiyuki Yoneda 《Journal of bone and mineral research》2008,23(6):907-914
Introduction: RANKL is known to be important not only for differentiation and activation of osteoclasts but also for their survival. Experimentally, apoptosis of osteoclasts is rapidly induced by the deprivation of RANKL. RANKL activates Elk‐related tyrosine kinase (ERK), p38, c‐Jun N‐terminal kinase (JNK), and NF‐κB pathways through TRAF6 in osteoclasts and the precursor cells. It has been shown that ERK is critical for regulation of osteoclast survival. However, an involvement of other RANKL signaling pathways such as JNK signaling in survival of osteoclasts has not been fully understood yet. Materials and Methods: Osteoclasts derived from primary mouse bone marrow cells by soluble RANKL (sRANKL) were treated with a JNK inhibitor, SP600125, or infected with adenovirus carrying dominant‐negative (DN)‐c‐jun, DN‐c‐fos, mitogen‐activated protein kinase kinase 1 (MEKK1), I‐κBα mutant, or NF‐κB components, p50 and p65. Osteoclasts were cultured with or without sRANKL, and apoptotic phenotype was determined by TUNEL assay, DAPI staining, and expression of cleaved caspase 3 followed by TRACP staining. Results: Overexpression of TRAF6 activated JNK and NF‐κB signaling pathways and clearly prevented osteoclasts from apoptosis caused by abrogation of sRANKL. An anti‐apoptotic effect of RANKL/RANK/TRAF6 signaling on osteoclast was inhibited by JNK‐specific inhibitor SP600125 and by overexpression of dominant‐negative JNK1, c‐jun, and c‐fos. Also, overexpression of MEKK1 inhibited apoptosis of osteoclasts even in the absence of sRANKL along with activation of JNK/c‐jun signaling. On the other hand, blockade of NF‐κB signaling by I‐κBα mutant or overexpression of NF‐κB components showed a marginal effect on apoptosis of osteoclasts. Conclusions: An important role of RANKL‐induced activation of MEKK1/JNK/c‐jun signaling in the regulation of apoptosis in osteoclasts was shown. Our study suggests that c‐fos plays a role as a partner of activator protein‐1 factor, c‐jun, during the regulation of apoptosis in osteoclasts. 相似文献
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Katelyn Paz Ryan Flynn Jing Du Stacey Tannheimer Amy J. Johnson Shuai Dong Anne‐Katrien Stark Klaus Okkenhaug Angela Panoskaltsis‐Mortari Peter T. Sage Arlene H. Sharpe Leo Luznik Jerome Ritz Robert J. Soiffer Corey S. Cutler John Koreth Joseph H. Antin David B. Miklos Kelli P. MacDonald Geoffrey R. Hill Ivan Maillard Jonathan S. Serody William J. Murphy David H. Munn Colby Feser Michael Zaiken Bart Vanhaesebroeck Laurence A. Turka John C. Byrd Bruce R. Blazar 《American journal of transplantation》2019,19(6):1820-1830
Chronic graft‐versus‐host disease (cGVHD) is a leading cause of morbidity and mortality following allotransplant. Activated donor effector T cells can differentiate into pathogenic T helper (Th)‐17 cells and germinal center (GC)–promoting T follicular helper (Tfh) cells, resulting in cGVHD. Phosphoinositide‐3‐kinase‐δ (PI3Kδ), a lipid kinase, is critical for activated T cell survival, proliferation, differentiation, and metabolism. We demonstrate PI3Kδ activity in donor T cells that become Tfh cells is required for cGVHD in a nonsclerodermatous multiorgan system disease model that includes bronchiolitis obliterans (BO), dependent upon GC B cells, Tfhs, and counterbalanced by T follicular regulatory cells, each requiring PI3Kδ signaling for function and survival. Although B cells rely on PI3Kδ pathway signaling and GC formation is disrupted resulting in a substantial decrease in Ig production, PI3Kδ kinase‐dead mutant donor bone marrow–derived GC B cells still supported BO cGVHD generation. A PI3Kδ‐specific inhibitor, compound GS‐649443, that has superior potency to idelalisib while maintaining selectivity, reduced cGVHD in mice with active disease. In a Th1‐dependent and Th17‐associated scleroderma model, GS‐649443 effectively treated mice with active cGVHD. These data provide a foundation for clinical trials of US Food and Drug Administration (FDA)–approved PI3Kδ inhibitors for cGVHD therapy in patients. 相似文献
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Zhenxi Li Yu Ma Lipeng Zhang Chunbing Zheng Wenwei Qiu Xian Wu Xiu Wang Hui Li Jie Tang Min Qian Dali Li Ping Wang Jian Luo Mingyao Liu 《Journal of bone and mineral research》2011,26(3):644-656
Activation of NF‐κB and MAPK/activator protein 1 (AP‐1) signaling pathways by receptor activator NF‐κB ligand (RANKL) is essential for osteoclast activity. Targeting NF‐κB and MAPK/AP‐1 signaling to modulate osteoclast activity has been a promising strategy for osteoclast‐related diseases. In this study we examined the effects of maslinic acid (MA), a pentacyclic triterpene acid that is widely present in dietary plants, on RANKL‐induced osteoclastogenesis, osteoclast function, and signaling pathways by in vitro and in vivo assay systems. In mouse bone marrow monocytes (BMMs) and RAW264.7 cells, MA inhibited RANKL‐induced osteoclastogenesis in a dose‐dependent manner within nongrowth inhibitory concentration, and MA decreased osteoclastogenesis‐related marker gene expression, including TRACP, MMP9, c‐Src, CTR, and cathepsin K. Specifically, MA suppressed osteoclastogenesis and actin ring formation at early stage. In ovariectomized mice, administration of MA prevented ovariectomy‐induced bone loss by inhibiting osteoclast activity. At molecular levels, MA abrogated the phosphorylation of MAPKs and AP‐1 activity, inhibited the IκBα phosphorylation and degradation, blocked NF‐κB/p65 phosphorylation, nuclear translocation, and DNA‐binding activity by downregulating RANK expression and blocking RANK interaction with TRAF6. Together our data demonstrate that MA suppresses RANKL‐induced osteoclastogenesis through NF‐κB and MAPK/AP‐1 signaling pathways and that MA is a promising agent in the treatment of osteoclast‐related diseases such as osteoporosis. © 2011 American Society for Bone and Mineral Research. 相似文献
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Activation of TLR signalling regulates microwave radiation‐mediated impairment of spermatogenesis in rat testis 下载免费PDF全文
Microwave radiation could increase the expression of pro‐inflammatory cytokines in rat Sertoli cells, which may impair spermatogenesis. However, the mechanisms that microwave radiation induces the cytokine expression in Sertoli cells remain to be clarified. The activation of TLRs by their ligands can trigger a common signalling pathway to upregulate inflammatory cytokines such as IL‐1, IL‐6, IL‐12 and TNF‐α. Microwave radiation can increase the expression of TLRs in lymphocytes. The purpose of this study was to determine the effect of microwave radiation on the TLRs in rat testis. We focus on the effect of TLR2‐5 (which is expressed relatively highly) by microwave radiation. The results showed that the expression of TLR2‐5 and the pro‐inflammatory cytokines (IL‐1β, IL‐6 and TNF‐α) was increased both in mRNA and in protein. Furthermore, p‐p38, p‐ERK1/2, p‐JNK and p‐NF‐κB p65, the key factors of TLR signalling, were also elevated by microwave exposure. And the NF‐κB can be induced more dominantly. These results suggest that TLRs signalling can be activated by microwave radiation in testis, which may provide the molecular basis for the in‐depth study. 相似文献
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Yi‐Chin Fong Ming‐Chei Maa Fuu‐Jen Tsai Wen‐Chi Chen Jaung‐Geng Lin Long‐Bin Jeng Rong‐Sen Yang Wen‐Mei Fu Chih‐Hsin Tang PhD 《Journal of bone and mineral research》2008,23(6):961-970
Introduction: The bone marrow microenvironment is further enriched by growth factors released during osteoclastic bone resorption. It has been reported that the chemokine interleukin (IL)‐8 is a potent and direct activator of osteoclastic differentiation and bone resorption. However, the effect of bone‐derived growth factors on the IL‐8 production in human cancer cells and the promotion of osteoclastogenesis are largely unknown. The aim of this study was to investigate whether osteoblast‐derived TGF‐β1 is associated with osteolytic bone diseases. Materials and Methods: IL‐8 mRNA levels were measured using RT‐PCR analysis. MAPK phosphorylation was examined using the Western blot method. siRNA was used to inhibit the expression of TGF‐β1, BMP‐2, and IGF‐1. DNA affinity protein‐binding assay and chromatin immunoprecipitation assays were used to study in vitro and in vivo binding of c‐fos, c‐jun, p65, and p50 to the IL‐8 promoter. A transient transfection protocol was used to examine IL‐8, NF‐κB, and activator protein (AP)‐1 activity. Results: Osteoblast conditioned medium (OBCM) induced activation of IL‐8, AP‐1, and NF‐κB promoter in human cancer cells. Osteoblasts were transfected with TGF‐β1, BMP‐2, or IGF‐1 small interfering RNA, and the medium was collected after 48 h. TGF‐β1 but not BMP‐2 or IGF‐1 siRNA inhibited OBCM‐induced IL‐8 release in human cancer cells. In addition, TGF‐β1 also directly induced IL‐8 release in human cancer cells. Activation of AP‐1 and NF‐κB DNA‐protein binding and MAPKs after TGF‐β1 treatment was shown, and TGF‐β1–induced IL‐8 promoter activity was inhibited by the specific inhibitors of MAPK cascades. Conclusions: In this study, we provide evidence to show that the osteoblasts release growth factors, including TGF‐β1, BMP‐2, and IGF‐1. TGF‐β1 is the major contributor to the activation of extracellular signal‐related kinase (ERK), p38, and c‐Jun N‐terminal kinase (JNK), leading to the activation of AP‐1 and NF‐κB on the IL‐8 promoter and initiation of IL‐8 mRNA and protein release, thereby promoting osteoclastogenesis. 相似文献
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Kate H. Gartlan Hemamalini Bommiasamy Katelyn Paz Andrew N. Wilkinson Mary Owen Dawn K. Reichenbach Tatjana Banovic Kimberly Wehner Faith Buchanan Antiopi Varelias Rachel D. Kuns Karshing Chang Yuri Fedoriw Thomas Shea James Coghill Michael Zaiken Maximilian W. Plank Paul S. Foster Andrew D. Clouston Bruce R. Blazar Jonathan S. Serody Geoffrey R. Hill 《American journal of transplantation》2018,18(4):810-820
Graft‐versus‐host disease (GVHD) is the major cause of nonrelapse morbidity and mortality after allogeneic stem cell transplantation (allo‐SCT). Prevention and treatment of GVHD remain inadequate and commonly lead to end‐organ dysfunction and opportunistic infection. The role of interleukin (IL)‐17 and IL‐22 in GVHD remains uncertain, due to an apparent lack of lineage fidelity and variable and contextually determined protective and pathogenic effects. We demonstrate that donor T cell–derived IL‐22 significantly exacerbates cutaneous chronic GVHD and that IL‐22 is produced by highly inflammatory donor CD4+ T cells posttransplantation. IL‐22 and IL‐17A derive from both independent and overlapping lineages, defined as T helper (Th)22 and IL‐22+ Th17 cells. Donor Th22 and IL‐22+ Th17 cells share a similar IL‐6–dependent developmental pathway, and while Th22 cells arise independently of the IL‐22+Th17 lineage, IL‐17 signaling to donor Th22 directly promotes their development in allo‐SCT. Importantly, while both IL‐22 and IL‐17 mediate skin GVHD, Th17‐induced chronic GVHD can be attenuated by IL‐22 inhibition in preclinical systems. In the clinic, high levels of both IL‐17A and IL‐22 expression are present in the skin of patients with GVHD after allo‐SCT. Together, these data demonstrate a key role for donor‐derived IL‐22 in patients with chronic skin GVHD and confirm parallel but symbiotic developmental pathways of Th22 and Th17 differentiation. 相似文献
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Brazilin blocks catabolic processes in human osteoarthritic chondrocytes via inhibition of NFKB1/p50 下载免费PDF全文
Daniela Weinmann Monika Mueller Sonja M. Walzer Gerhard M. Hobusch Richard Lass Claudia Gahleitner Helmut Viernstein Reinhard Windhager Stefan Toegel 《Journal of orthopaedic research》2018,36(9):2431-2438
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Q. Gao L. L. Ma X. Gao W. Yan P. Williams D. P. Yin 《American journal of transplantation》2010,10(7):1588-1596
We have previously shown that islet emboli in the portal vein block blood flow and induce local inflammatory reaction, resulting in functional loss of islet grafts following intraportal transplantation. This study was designed to test whether Toll‐like receptor (TLR) activation mediates early islet graft failure. Syngeneic islet grafts were transplanted into chemically induced diabetic mice, and TLR deficient mice were used as donors and/or recipients of islet grafts. Islet viability, proinflammatory cytokines, high‐mobility group box‐1 (HMGB1) and NF‐κB activation were analyzed by bioluminesce imaging (BLI), quantitative RT‐PCR (qRT‐PCR) and histology. Early islet graft failure was observed in mice with intraportal islet engrafts with increased proinflammatory cytokines, HMGB1 expression, NF‐κB activation, caspase‐3 and TUNEL positive cells. Deficiency of TLR4 in donor, but not in recipient, inhibited NF‐κB activation, reduced proinflammatory cytokines and improved viability of islet grafts. Blockade of HMGB1 with anti‐HMGB1 monoclonal antibody (mAb, 2g7) inhibited inflammatory reactions, as evidenced by reduced TNFα and IL‐1ß production, and improved islet viability. We conclude that TLR4 activation mediates early graft failure following intraportal islet transplantation. Inhibition of TLR4 activation represents a novel strategy to attenuate early graft failure following intraportal islet transplantation. 相似文献
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p120‐Catenin modulating nuclear factor‐κB activation is partially RhoA/ROCKdependent in scratch injury 下载免费PDF全文
Shenghui Qin MD Lingzhi Qin MD Chao Zhang MD Liwei Liu MD Wenjia Sun MS Naping Li BS Renliang Wu BS Xi Wang MD PhD 《Wound repair and regeneration》2015,23(2):231-240
p120‐catenin (p120) is known as a cadherin‐associated protein that participates in tumor metastasis and invasion, as well as an anti‐inflammatory mediator. Recently, its anti‐inflammatory role is drawing increasing attention, but the regulatory mechanisms are still unknown. Here, we report that p120 modulated inflammatory responses partially depends on RhoA/ROCK pathway in scratch‐induced injury in human bronchial epithelial cells (BECs). For the first time, we found that p120 was significantly reduced in BECs after scratching, which could induce interleukin‐8 (IL‐8) production through nuclear factor‐κB (NF‐κB) activation accompanied with IκBα phosphorylation. Over‐expression of p120 3A could inhibit NF‐κB activation and IL‐8 mRNA expression and protein synthesis after scratching, while p120 knockdown by small interfering RNA could promote NF‐κB activation and IL‐8 mRNA expression and protein synthesis after scratching. Furthermore, we found that RhoA was the binding partner of p120 in BECs. Although total RhoA and p120‐binded RhoA remained unchanged, the RhoA activity was increased after scratching. Chemical blockade of RhoA/ROCK signaling (Y27632) inhibited scratch‐induced nuclear translocation of NF‐κB p65. Over‐expression of p120 3A attenuated scratch‐induced RhoA activation, whereas silence of p120 significantly elevated scratch‐induced RhoA activation in BCEs. Conclusively, these results indicate an anti‐inflammatory effect of p120 in bronchial epithelial cells through its modulation of NF‐κB signaling depending on RhoA/ROCK pathway. 相似文献
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Dereen Najat Thomas Garner Thilo Hagen Barry Shaw Paul W Sheppard Alberto Falchetti Francesca Marini Maria L Brandi Jed E Long James R Cavey Mark S Searle Robert Layfield 《Journal of bone and mineral research》2009,24(4):632-642
Mutations affecting the ubiquitin‐associated (UBA) domain of sequestosome 1 (SQSTM1/p62) are commonly found in Paget's disease of bone (PDB) and impair SQSTM1's ability to bind ubiquitin, resulting in dysregulated NF‐κB signaling. In contrast, non‐UBA domain mutations are rarer, and little is known about how they manifest their effects. We present the first characterization at the molecular, cellular, and functional level of a non‐UBA domain missense mutation (A381V) of SQSTM1. Direct sequencing of exon 7 of the SQSTM1 gene in an Italian PDB patient detected a heterozygous C to T transversion at position 1182, resulting in an alanine to valine substitution at codon 381. Pull‐down assays showed the non‐UBA region of SQSTM1 that contains A381 is important in mediating ubiquitin‐binding affinity and that the A381V mutation exerts weak negative effects on ubiquitin binding. Structural and binding analyses of longer UBA constructs containing A381, using NMR spectroscopy and circular dichroism, showed this region of the protein to be largely unstructured and confirmed its contribution to increased ubiquitin‐binding affinity. Co‐transfections of U20S cells showed that the A381V mutant SQSTM1 co‐localized with ubiquitin with a cellular phenotype indistinguishable from wildtype. Finally, effects of the wildtype and mutant SQSTM1 on NF‐κB signaling were assessed in HEK293 cells co‐transfected with an NF‐κB luciferase reporter construct. A381V mutant SQSTM1 produced a level of activation of NF‐κB signaling greater than wildtype and similar to that of UBA domain mutants, indicating that non‐UBA and UBA domain mutations may exert their effects through a common mechanism involving dysregulated NF‐κB signaling. 相似文献
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Silent information regulator (Sir)T1 inhibits NF‐κB signaling to maintain normal skeletal remodeling
James R Edwards Daniel S Perrien Nicole Fleming Jeffry S Nyman Koichiro Ono Linda Connelly Megan M Moore Seint T Lwin Fiona E Yull Gregory R Mundy Florent Elefteriou 《Journal of bone and mineral research》2013,28(4):960-969
Silent information regulator T1 (SirT1) is linked to longevity and negatively controls NF‐κB signaling, a crucial mediator of survival and regulator of both osteoclasts and osteoblasts. Here we show that NF‐κB repression by SirT1 in both osteoclasts and osteoblasts is necessary for proper bone remodeling and may contribute to the mechanisms linking aging and bone loss. Osteoclast‐ or osteoblast‐specific SirT1 deletion using the Sirtflox/flox mice crossed to lysozyme M‐cre and the 2.3 kb col1a1‐cre transgenic mice, respectively, resulted in decreased bone mass caused by increased resorption and reduced bone formation. In osteoclasts, lack of SirT1 promoted osteoclastogenesis in vitro and activated NF‐κB by increasing acetylation of Lysine 310. Importantly, this increase in osteoclastogenesis was blocked by pharmacological inhibition of NF‐κB. In osteoblasts, decreased SirT1 reduced osteoblast differentiation, which could also be rescued by inhibition of NF‐κB. In further support of the critical role of NF‐κB signaling in bone remodeling, elevated NF‐κB activity in IκBα+/? mice uncoupled bone resorption and formation, leading to reduced bone mass. These findings support the notion that SirT1 is a genetic determinant of bone mass, acting in a cell‐autonomous manner in both osteoblasts and osteoclasts, through control of NF‐κB and bone cell differentiation. © 2013 American Society for Bone and Mineral Research. 相似文献
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M. Schuchmann R. G. Meyer E. Distler E. Von Stebut J. Kuball E. Schnürer T. Wölfel M. Theobald A. Konur S. Gregor O. Schreiner C. Huber P. R. Galle G. Otto W. Herr 《American journal of transplantation》2008,8(11):2434-2444
Acute graft‐versus‐host disease (aGVHD) is a life‐threatening complication after solid‐organ transplantation, which is mediated by host‐reactive donor T cells emigrating from the allograft. We report on two liver transplant recipients who developed an almost complete donor chimerism in peripheral blood and bone marrow‐infiltrating T cells during aGVHD. By analyzing these T cells directly ex vivo, we found that they died by apoptosis over time without evidence of rejection by host T cells. The host‐versus‐donor reactivity was selectively impaired, as anti‐third‐party and antiviral T cells were still detectable in the host repertoire. These findings support the acquired donor‐specific allotolerance concept previously established in animal transplantation studies. We also observed that the resolution of aGVHD was not accompanied by an expansion of circulating immunosuppressive CD4/CD25/FoxP3‐positive T cells. In fact, graft‐versus‐host‐reactive T cells were controlled by an alternative negative regulatory pathway, executed by the programmed death (PD)‐1 receptor and its ligand PD‐L1. We found high PD‐1 expression on donor CD4 and CD8 T cells. In addition, blocking PD‐L1 on host‐derived cells significantly enhanced alloreactivity by CD8 T cells in vitro. We suggest the interference with the PD‐1/PD‐L1 pathway as a therapeutic strategy to control graft‐versus‐host‐reactive T cells in allograft recipients. 相似文献
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H. Zhao H. R. Watts M. Chong H. Huang C. Tralau‐Stewart P. H. Maxwell M. Maze A. J. T. George D. Ma 《American journal of transplantation》2013,13(8):2006-2018
Prolonged hypothermic storage causes ischemia‐reperfusion injury (IRI) in the renal graft, which is considered to contribute to the occurrence of the delayed graft function (DGF) and chronic graft failure. Strategies are required to protect the graft and to prolong renal graft survival. We demonstrated that xenon exposure to human proximal tubular cells (HK‐2) led to activation of range of protective proteins. Xenon treatment prior to or after hypothermia–hypoxia challenge stabilized the HK‐2 cellular structure, diminished cytoplasmic translocation of high‐mobility group box (HMGB) 1 and suppressed NF‐κB activation. In the syngeneic Lewis‐to‐Lewis rat model of kidney transplantation, xenon exposure to donors before graft retrieval or to recipients after engraftment decreased caspase‐3 expression, localized HMGB‐1 within nuclei and prevented TLR‐4/NF‐κB activation in tubular cells; serum pro‐inflammatory cytokines IL‐1β, IL‐6 and TNF‐α were reduced and renal function was preserved. Xenon treatment of graft donors or of recipients prolonged renal graft survival following IRI in both Lewis‐to‐Lewis isografts and Fischer‐to‐Lewis allografts. Xenon induced cell survival or graft functional recovery was abolished by HIF‐1α siRNA. Our data suggest that xenon treatment attenuates DGF and enhances graft survival. This approach could be translated into clinical practice leading to a considerable improvement in long‐term graft survival. 相似文献
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《Journal of orthopaedic research》2017,35(2):281-288