共查询到20条相似文献,搜索用时 308 毫秒
1.
Michael R. Pranzatelli Elizabeth D. Tate Nathan R. McGee Jerry A. Colliver Richard M. Ransohoff 《Journal of clinical immunology》2013,33(4):817-825
Purpose
To study the role of Th2-attracting chemokines in opsoclonus-myoclonus syndrome (OMS), a serious neurological paraneoplastic disorder in need of better immunological understanding and therapy.Methods
The CCR4 agonists CCL22 and CCL17 were measured in serum by ELISA in children with OMS (238 and 260, respectively), pediatric controls (115 and 143), and other inflammatory neurological disorders (33 and 24).Results
Both CCL22 (+55 %) and CCL17 (+121 %) were significantly elevated in untreated OMS compared to controls and inter-correlated (p?<?0.0001). Their concentrations in untreated OMS also were higher than in OIND (21 %, 41 %). The concentration of CCL22 in ACTH and steroids groups (not IVIg) was 51 % lower than in controls, but only a smaller effect of ACTH on CCL17 was found. Prospective longitudinal studies revealed a precipitous 81 % drop in CCL22 even by the first week of high-dose ACTH therapy, staying below control mean for at least 12 weeks, and a 34 % reduction after 8 months of combined treatment. Response to ACTH was dose-related (r?=??0.50, p?<?0.0001). Luminex detection confirmed the ELISA results for CCL22, which were about 200 % higher.Conclusions
These data reveal an elevated serum concentration of Th2-attracting chemokines CCL22 and CCL17 in OMS. Marked and rapid reduction in CCL22, not CCL17, with either ACTH or steroid therapy suggests differential regulation and cellular sources of CCR4 ligands, and CCL22 as a potential candidate biomarker for ACTH or corticosteroid effect. 相似文献2.
Astrid Rohrbeck Judith Neukirchen Michael Rosskopf Guillermo G Pardillos Helene Geddert Andreas Schwalen Helmut E Gabbert Arndt von Haeseler Gerald Pitschke Matthias Schott Ralf Kronenwett Rainer Haas Ulrich-Peter Rohr 《Journal of translational medicine》2008,6(1):1-17
Background
Our previous studies have demonstrated that transduction of human dendritic cells (DC) with adenovirus encoding secondary lymphoid chemokine, CCL21, led to secretion of biologically active CCL21 without altering DC phenotype or viability. In addition, intratumoral injections of CCL21-transduced DC into established murine lung tumors resulted in complete regression and protective anti-tumor immunity. These results have provided the rationale to generate a clinical grade adenoviral vector encoding CCL-21 for ex vivo transduction of human DC in order to assess intratumoral administration in late stage human lung cancer.Methods
In the current study, human monocyte-derived DC were differentiated by exposure to GM-CSF and IL-4 from cryopreserved mononuclear cells obtained from healthy volunteers. Transduction with clinical grade adenoviral vector encoding CCL21 (1167 viral particles per cell) resulted in secretion of CCL21 protein.Results
CCL21 protein production from transduced DC was detected in supernatants (24–72 hours, 3.5–6.7 ng/4–5 × 106 cells). DC transduced with the clinical grade adenoviral vector were > 88% viable (n = 16), conserved their phenotype and maintained integral biological activities including dextran uptake, production of immunostimulatory cytokines/chemokines and antigen presentation. Furthermore, supernatant from CCL21-DC induced the chemotaxis of T2 cells in vitro.Conclusion
Viable and biologically active clinical grade CCL21 gene-modified DC can be generated from cryopreserved PBMC. 相似文献3.
Kanako Kitahara Natsuko Kusunoki Hiroshi Takahashi Kazuaki Tsuchiya Shinichi Kawai 《Inflammation research》2012,61(12):1385-1394
Objective
Although the effects of tacrolimus on T cells are well-known, direct effects on rheumatoid synovial fibroblasts (RSF) remain unclear. We studied the effects of tacrolimus on RSF by a DNA microarray analysis.Materials and methods
Tacrolimus and interleukin (IL)-1β were added to cultured RSF. Total RNA was prepared from the cells and the gene expression profile was analyzed by a DNA microarray screening system. mRNA expressions influenced by tacrolimus in the screening system were confirmed by real-time PCR. The effects of tacrolimus on nuclear translocation of nuclear factor-κB (NF-κB) were also examined.Results
The mRNA expressions of CCL3, CCL4, and CXCL8 were up-regulated by IL-1β and down-regulated by tacrolimus. The levels of these IL-1β-induced chemokines in culture supernatant were decreased by a therapeutic concentration of tacrolimus. Tumor necrosis factor-α as well as IL-1β induced these chemokines, while tacrolimus inhibited their production and mRNA expression. Chemotaxis of polymorphonuclear cells in response to IL-1β was also inhibited by tacrolimus. Nuclear translocation of p50 and p65 NF-κB in response to IL-1β was decreased by tacrolimus.Conclusion
IL-1β-induced chemokine expressions were down-regulated by tacrolimus, suggesting that tacrolimus exerts its anti-inflammatory effect partly through inhibiting chemokine production by RSF. 相似文献4.
Anita Thyagarajan-Sahu Brandon Lane Daniel Sliva 《BMC complementary and alternative medicine》2011,11(1):1-14
Background
Clinical studies have shown that rose hip powder (RHP) alleviates osteoarthritis (OA). This might be due to anti-inflammatory and cartilage-protective properties of the complete RHP or specific constituents of RHP. Cellular systems (macrophages, peripheral blood leukocytes and chondrocytes), which respond to inflammatory and OA-inducing stimuli, are used as in vitro surrogates to evaluate the possible pain-relief and disease-modifying effects of RHP.Methods
(1) Inflammatory processes were induced in RAW264.7 cells or human peripheral blood leukocytes (PBL) with LPS. Inflammatory mediators (nitric oxide (NO), prostaglandin E2 (PGE2) and cytokines/chemokines) were determined by the Griess reaction, EIA and multiplex ELISA, respectively. Gene expression was quantified by RT-PCR. RHP or its constituent galactolipid, GLGPG (galactolipid (2S)-1, 2-di-O-[(9Z, 12Z, 15Z)-octadeca-9, 12, 15-trienoyl]-3-O-β-D-galactopyranosyl glycerol), were added at various concentrations and the effects on biochemical and molecular parameters were evaluated. (2) SW1353 chondrosarcoma cells and primary human knee articular chondrocytes (NHAC-kn) were treated with interleukin (IL)-1β to induce in vitro processes similar to those occurring during in vivo degradation of cartilage. Biomarkers related to OA (NO, PGE2, cytokines, chemokines, metalloproteinases) were measured by multiplex ELISA and gene expression analysis in chondrocytes. We investigated the modulation of these events by RHP and GLGPG.Results
In macrophages and PBL, RHP and GLGPG inhibited NO and PGE2 production and reduced the secretion of cytokines (TNF-α, IFN-γ, IL-1β, IL-6, IL-12) and chemokines (CCL5/RANTES, CXCL10/IP-10). In SW1353 cells and primary chondrocytes, RHP and GLGPG diminished catabolic gene expression and inflammatory protein secretion as shown by lower mRNA levels of matrix metalloproteinases (MMP-1, MMP-3, MMP-13), aggrecanase (ADAMTS-4), macrophage inflammatory protein (MIP-2, MIP-3α), CCL5/RANTES, CXCL10/IP-10, IL-8, IL-1α and IL-6. The effects of GLGPG were weaker than those of RHP, which presumably contains other chondro-protective substances besides GLGPG.Conclusions
RHP and GLGPG attenuate inflammatory responses in different cellular systems (macrophages, PBLs and chondrocytes). The effects on cytokine production and MMP expression indicate that RHP and its constituent GLGPG down-regulate catabolic processes associated with osteoarthritis (OA) or rheumatoid arthritis (RA). These data provide a molecular and biochemical basis for cartilage protection provided by RHP. 相似文献5.
Positive Correlation of STAT1 and miR-146a with Anemia in Patients with Systemic Lupus Erythematosus
Paul R. Dominguez-Gutierrez Angela Ceribelli Minoru Satoh Eric S. Sobel Westley H. Reeves Edward K. L. Chan 《Journal of clinical immunology》2014,34(2):171-180
Purpose
Anemia is one of the most common hematological manifestations in SLE patients, occurring in about 50 % of active cases. STAT1 is a critical signaling molecule required for the production of type-1 interferon (I-IFN), CCL2, and CXCL10, all of which are upregulated in SLE. Overexpression of STAT1 has been described to be involved in anemia in animal models. The aim of this study is to analyze how these components are involved in SLE-associated anemia.Methods
Blood samples were collected from 39 healthy donors and 101 SLE patients fulfilling ACR criteria. Samples were collected from a total of 180 visits (58 patients had 2 or more visits) of which 52 visits included a diagnosis of anemia. Healthy donors had only single visit. Total RNA, isolated from leukocytes, was analyzed by Taqman qPCR. Relative expression levels of I-IFN signature genes, chemokines, and miR-146a were determined by the ΔΔCT method. Results were correlated with clinical data and analyzed by the Wilcoxon/Kruskal-Wallis test and Fisher’s exact test.Results
Significant increases in IFN score (p?<?0.0001), STAT1 (p?<?0.0001), miR-146a (p?<?0.0005), CCL2 (p?=?0.0047), and CXCL10 (p?=?0.017), as well as a significant decrease in pri-miR-146a (p?=?0.0002), were detected in the anemic SLE patient visits (n?=?52) compared to non-anemic SLE visits (n?=?128). Regardless of disease activity, lupus nephritis, or race, anemic SLE patients displayed significantly elevated levels of STAT1 and miR-146a compared to non-anemic SLE patients.Conclusions
STAT1 and miR-146a may be upregulated during inflammation and via proinflammatory cytokines and chemokines in SLE. Prolonged upregulation of STAT1 and miR-146a appears to play an important role in anemia in SLE patients. 相似文献6.
Gaël Mouillot Maryvonnick Carmagnat Laurence Gérard Jean-Luc Garnier Claire Fieschi Nicolas Vince Lionel Karlin Jean-François Viallard Roland Jaussaud Julien Boileau Jean Donadieu Martine Gardembas Nicolas Schleinitz Felipe Suarez Eric Hachulla Karen Delavigne Martine Morisset Serge Jacquot Nicolas Just Lionel Galicier Dominique Charron Patrice Debré Eric Oksenhendler Claire Rabian 《Journal of clinical immunology》2010,30(5):746-755
Background
Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by recurrent infections and defective immunoglobulin production.Methods
The DEFI French national prospective study investigated peripheral T-cell and B-cell compartments in 313 CVID patients grouped according to their clinical phenotype, using flow cytometry.Results
In patients developing infection only (IO), the main B-cell or T-cell abnormalities were a defect in switched memory B cells and a decrease in naive CD4+ T cells associated with an increase in CD4+CD95+ cells. These abnormalities were more pronounced in patients developing lymphoproliferation (LP), autoimmune cytopenia (AC), or chronic enteropathy (CE). Moreover, LP and AC patients presented an increase in CD21low B cells and CD4+HLA-DR+ T cells and a decrease in regulatory T cells.Conclusion
In these large series of CVID patients, the major abnormalities of the B-cell and T-cell compartments, although a hallmark of CVID, were only observed in half of the IO patients and were more frequent and severe in patients with additional lymphoproliferative, autoimmune, and digestive complications. 相似文献7.
Salvatore Chirumbolo Guido Franceschetti Elena Zoico Clara Bambace Luciano Cominacini Mauro Zamboni 《Inflammation research》2014,63(6):495-507
Objective
In vitro 3T3-L1 mouse cells represent a reliable model to investigate the inflammatory phenotype of adipocytes activated by bacteria-derived lipopolysaccharide (LPS). In this study we have evaluated the differential expression of adipokines in response to increasing doses of LPS and various incubation times.Methods
3T3-L1 mouse adipocytes were treated with E. coli LPS (from 0 to 10 μg/ml) for a time course ranging from 4 to 24 h, 4 h each. A time point at 2 h was also included to highlight early activation by LPS. mRNA expression by RT-PCR on cell lysates and ELISA assays on cell culture supernatants were performed.Results
Cells activated by increasing doses of LPS upregulated TNF-α expression in the first 2 h, but this expression slowed down within 6–8 h, while IL-6 expression was increasing. This reduction was also observed for CXCL12/SDF1α. Unlike IL-10, IL-6 expression was constantly upregulated by prolonging incubation with LPS. TNF-α and CXCL12 gene expression occurred early in the time-course and exhibited a second increase following the first 4–6 h of incubation with LPS. Optimal expression of most adipokines needed 6–8 h of a prolonged treatment with LPS at 37 °C. The chemokines MIP-1α/CCL3 and MIP-1β/CCL4 were maximally expressed within the first 8 h, then significantly reduced in the following times. IL-10 expression was upregulated by low doses of LPS and downregulated by prolonging time with the bacterial endotoxin. ELISA analysis of released products generally confirmed the result from gene expression experiments.Conclusion
These data, while assessing previously reported results, highlighted new evidence about the time-dependency in LPS-mediated adipokine production, thus contributing to the comprehension of the inflammatory response of adipocyte. 相似文献8.
Lothar Marischen Anne Englert Anna-Lena Schmitt Hermann Einsele Juergen Loeffler 《BMC immunology》2018,19(1):39
Background
The saprophytic fungus Aspergillus fumigatus reproduces by generation of conidia, which are spread by airflow throughout nature. Since humans are inhaling certain amounts of spores every day, the (innate) immune system is constantly challenged. Even though macrophages and neutrophils carry the main burden, also NK cells are regarded to contribute to the antifungal immune response. While NK cells reveal a low frequency, expression and release of immunomodulatory molecules seem to be a natural way of their involvement.Results
In this study we show, that NK cells secrete chemokines such as CCL3/MIP-1α, CCL4/MIP-1β and CCL5/RANTES early on after stimulation with Aspergillus fumigatus and, in addition, adjust the concentration of chemokines released to the multiplicity of infection of Aspergillus fumigatus.Conclusions
These results further corroborate the relevance of NK cells within the antifungal immune response, which is regarded to be more and more important in the development and outcome of invasive aspergillosis in immunocompromised patients after hematopoietic stem cell transplantation. Additionally, the correlation between the multiplicity of infection and the expression and release of chemokines shown here may be useful in further studies for the quantification and/or surveillance of the NK cell involvement in antifungal immune responses.9.
Objective
A low pH microenvironment is a characteristic feature of inflammation loci and affects the functions of immune cells. In this study, we investigated the effect of extracellular acidification on macrophage gene expression.Methods
RAW264.7 macrophages were incubated in neutral (pH 7.4) or acidic (pH 6.8) medium for 4 h. Global mRNA expression levels were determined using Affymetrix genechips.Results
The mRNA expressions of 353 macrophage genes were significantly modified after incubation in acidic medium; 193 were up-regulated and 160 down-regulated. Differentially regulated genes were grouped into 13 classes based on the functions of the corresponding protein products. Pathway analysis revealed that differentially expressed genes are enriched in pathways related to inflammation and immune responses. Quantitative real-time PCR analysis confirmed that the expressions of CXCL10, CXCL14, IL-18, IL-4RA, ABCA1, CCL4, IL-7R, CXCR4, TLR7, and CCL3 mRNAs were regulated by extracellular acidification.Conclusion
The results of this study provide insights into the effects of acidic extracellular environments on macrophage gene expression. 相似文献10.
The thymus plays a primary role in early-onset Myasthenia Gravis (MG) mediated by anti-acetylcholine receptor (AChR) antibodies. As we recently showed an inflammatory and anti-viral signature in MG thymuses, we investigated in detail the contribution of interferon (IFN)-I and IFN-III subtypes in thymic changes associated with MG. We showed that IFN-I and IFN-III subtypes, but especially IFN-β, induced specifically α-AChR expression in thymic epithelial cells (TECs). We also demonstrated that IFN-β increased TEC death and the uptake of TEC proteins by dendritic cells.In parallel, we showed that IFN-β increased the expression of the chemokines CXCL13 and CCL21 by TECs and lymphatic endothelial cells, respectively. These two chemokines are involved in germinal center (GC) development and overexpressed in MG thymus with follicular hyperplasia. We also demonstrated that the B-cell activating factor (BAFF), which favors autoreactive B-cells, was overexpressed by TECs in MG thymus and was also induced by IFN-β in TEC cultures.Some of IFN-β effects were down-regulated when cell cultures were treated with glucocorticoids, a treatment widely used in MG patients that decreases the number of thymic GCs.Similar changes were observed in vivo. The injections of Poly(I:C) to C57BL/6 mice triggered a thymic overexpression of IFN-β and IFN-α2 associated with increased expressions of CXCL13, CCL21, BAFF, and favored the recruitment of B cells. These changes were not observed in the thymus of IFN-I receptor KO mice injected with Poly(I:C), even if IFN-β and IFN-α2 were overexpressed.Altogether, these results demonstrate that IFN-β could play a central role in thymic events leading to MG by triggering the overexpression of α-AChR probably leading to thymic DC autosensitization, the abnormal recruitment of peripheral cells and GC formation. 相似文献
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12.
Baosheng Ge Jiqiang Li Zhijin Wei Tingting Sun Yanzhuo Song Naseer Ullah Khan 《BMC immunology》2017,18(1):54
Background
Chemokines and their cognate receptors play important role in the control of leukocyte chemotaxis, HIV entry and other inflammatory diseases. Developing an effcient method to investigate the functional expression of chemokines and its interactions with specific receptors will be helpful to asses the structural and functional characteristics as well as the design of new approach to therapeutic intervention.Results
By making systematic optimization study of expression conditions, soluble and functional production of chemokine C-C motif ligand 8 (CCL8) in Escherichia coli (E. coli) has been achieved with approx. 1.5 mg protein/l culture. Quartz crystal microbalance (QCM) analysis exhibited that the purified CCL8 could bind with C-C chemokine receptor type 3 (CCR3) with dissociation equilibrium constant (K D) as 1.2?×?10?7 M in vitro. Obvious internalization of CCR3 in vivo could be detected in 1 h when exposed to 100 nM of CCL8. Compared with chemokine C-C motif ligand 11 (CCL11) and chemokine C-C motif ligand 24 (CCL24), a weaker chemotactic effect of CCR3 expressing cells was observed when induced by CCL8 with same concentration.Conclusion
This study delivers a simple and applicable way to produce functional chemokines in E. coli. The results clearly confirms that CCL8 can interact with chemokine receptor CCR3, therefore, it is promising area to develop drugs for the treatment of related diseases.13.
Annemieke Geluk Krista E. van Meijgaarden Louis Wilson Kidist Bobosha Jolien J. van der Ploeg-van Schip Susan J. F. van den Eeden Edwin Quinten Karin Dijkman Kees L. M. C. Franken Elisabeth M. Haisma Mariëlle C. Haks Colette L. M. van Hees Tom H. M. Ottenhoff 《Journal of clinical immunology》2014,34(2):245-255
Purpose
Leprosy, a chronic disease initiated by Mycobacterium leprae, is often complicated by acute inflammatory reactions. Although such episodes occur in at least 50 % of all leprosy patients and may cause irreversible nerve damage, no laboratory tests are available for early diagnosis or prediction of reactions. Since immune- and genetic host factors are critical in leprosy reactions, we hypothesize that identification of host-derived biomarkers correlated to leprosy reactions can provide the basis for new tests to facilitate timely diagnosis and treatment thereby helping to prevent tissue damage.Methods
The longitudinal host response of a leprosy patient, who was affected by a type 1 reaction (T1R) after MDT-treatment, was studied in unprecedented detail, measuring cellular and humoral immunity and gene expression profiles to identify biomarkers specific for T1R.Results
Cytokine analysis in response to M. leprae revealed increased production of IFN-γ, IP-10, CXCL9, IL-17A and VEGF at diagnosis of T1R compared to before T1R, whereas a simultaneous decrease in IL-10 and G-CSF was observed at T1R. Cytokines shifts coincided with a reduction in known regulatory CD39+CCL4+ and CD25high T-cell subsets. Moreover, RNA expression profiles revealed that IFN-induced genes, (V)EGF, and genes associated with cytotoxic T-cell responses (GNLY, GZMA/B, PRF1) were upregulated during T1R, whereas expression of T-cell regulation-associated genes were decreased.Conclusions
These data show that increased inflammation, vasculoneogenesis and cytotoxicity, perturbed T-cell regulation as well as IFN-induced genes play an important role in T1R and provide potential T1R-specific host biomarkers. 相似文献14.
Chian-Jiun Liou Pei-Yun Cheng Wen-Chung Huang Cheng-Chi Chan Meng-Chun Chen Ming-Ling Kuo Jiann-Jong Shen 《Allergy, asthma & immunology research》2014,6(6):548-557
Purpose
Lovastatin is an effective inhibitor of cholesterol synthesis. A previous study demonstrated that lovastatin can also suppress airway hyperresponsiveness (AHR) in murine model of asthma. We aimed to investigate the effect of lovastatin on mucus secretion and inflammation-associated gene expression in the lungs of murine model of asthma.Methods
Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) by intraperitoneal injection, and orally administered lovastatin from days 14 to 27 post-injection. Gene expression in lung tissues was analyzed using real-time polymerase chain reaction. AHR and goblet cell hyperplasia were also examined. BEAS-2B human bronchial epithelial cells were used to evaluate the effect of lovastatin on the expression of cell adhesion molecules, chemokines, and proinflammatory cytokines in vitro.Results
We showed that lovastatin inhibits the expression of Th2-associated genes, including eotaxins and adhesion molecules, in the lungs of murine model of asthma. Mucin 5AC expression, eosinophil infiltration and goblet cell hyperplasia were significantly decreased in the lung tissue of murine model of asthma treated with lovastatin. Furthermore, lovastatin inhibited AHR and expression of Th2-associated cytokines in bronchoalveolar lavage fluid. However, a high dose (40 mg/kg) of lovastatin was required to decrease specific IgE to OVA levels in serum, and suppress the expression of Th2-associated cytokines in splenocytes. Activated BEAS-2B cells treated with lovastatin exhibited reduced IL-6, eotaxins (CCL11 and CCL24), and intercellular adhesion molecule-1 protein expression. Consistent with this, lovastatin also suppressed the ability of HL-60 cells to adhere to inflammatory BEAS-2B cells.Conclusions
These data suggest that lovastatin suppresses mucus secretion and airway inflammation by inhibiting the production of eotaxins and Th2 cytokines in murine model of asthma. 相似文献15.
Lara Kular Cyril Rivat Brigitte Lelongt Claire Calmel Maryvonne Laurent Michel Pohl Patrick Kitabgi Stéphane Melik-Parsadaniantz Cécile Martinerie 《Journal of neuroinflammation》2012,9(1):1-20
Background
Sustained neuroinflammation strongly contributes to the pathogenesis of pain. The clinical challenge of chronic pain relief led to the identification of molecules such as cytokines, chemokines and more recently matrix metalloproteinases (MMPs) as putative therapeutic targets. Evidence points to a founder member of the matricial CCN family, NOV/CCN3, as a modulator of these inflammatory mediators. We thus investigated the possible involvement of NOV in a preclinical model of persistent inflammatory pain.Methods
We used the complete Freund's adjuvant (CFA)-induced model of persistent inflammatory pain and cultured primary sensory neurons for in vitro experiments. The mRNA expression of NOV and pro-inflammatory factors were measured with real-time quantitative PCR, CCL2 protein expression was assessed using ELISA, MMP-2 and -9 activities using zymography. The effect of drugs on tactile allodynia was evaluated by the von Frey test.Results
NOV was expressed in neurons of both dorsal root ganglia (DRG) and dorsal horn of the spinal cord (DHSC). After intraplantar CFA injection, NOV levels were transiently and persistently down-regulated in the DRG and DHSC, respectively, occurring at the maintenance phase of pain (15 days). NOV-reduced expression was restored after treatment of CFA rats with dexamethasone. In vitro, results based on cultured DRG neurons showed that siRNA-mediated inhibition of NOV enhanced IL-1??- and TNF-??-induced MMP-2, MMP-9 and CCL2 expression whereas NOV addition inhibited TNF-??-induced MMP-9 expression through ??1 integrin engagement. In vivo, the intrathecal delivery of MMP-9 inhibitor attenuated mechanical allodynia of CFA rats. Importantly, intrathecal administration of NOV siRNA specifically led to an up-regulation of MMP-9 in the DRG and MMP-2 in the DHSC concomitant with increased mechanical allodynia. Finally, NOV intrathecal treatment specifically abolished the induction of MMP-9 in the DRG and, MMP-9 and MMP-2 in the DHSC of CFA rats. This inhibitory effect on MMP is associated with reduced mechanical allodynia.Conclusions
This study identifies NOV as a new actor against inflammatory pain through regulation of MMPs thus uncovering NOV as an attractive candidate for therapeutic improvement in pain relief. 相似文献16.
17.
A Novel Double-Enhanced Suicide Gene Therapy in a Colon Cancer Cell Line Mediated by Gef and Apoptin
Houria Boulaiz Antonia Aránega Cáceres Blanca Alvarez Pablo Rodríguez-Serrano Fernando Carrillo Esmeralda Melguizo Consolación Prados Jose 《BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy》2014,28(1):63-74
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Nakken B Munthe LA Konttinen YT Sandberg AK Szekanecz Z Alex P Szodoray P 《Autoimmunity reviews》2011,11(1):28-34
Rheumatoid arthritis (RA) is a chronic, autoimmune disease that affects primarily the joints and without proper treatment results in their progressive destruction. In addition to T-cells, B-cells play a central role in the pathogenesis of this disease. The synovial tissue is an active site of B-cell accumulation, plasma cell differentiation and in situ antibody-production in RA. As part of the complex role of B-cells in the joints and synovial membrane of RA patients, B cells secrete chemokines and cytokines and may function as antigen presenting cells. The multifaceted pathogenic function of B-cells identifies them as excellent targets for immunosuppressive therapy. B-cell targeting involves a wide spectrum of molecules, for example the B-cell antigen CD20 that allows specific and effective B-cell depletion. Another target, CD79, expressed by B-cell and plasma cell precursors is an obvious candidate that induces apoptosis as well as inhibition of B-cell receptor (BCR) activation and possibly depletion of ectopic germinal centers (GC). Inhibition of B-cell co-stimulatory molecules such as CD40, CD80/86 and ICOS, can lead to diminished B-cell activation. Moreover, anti-chemokine and anti-cytokine therapies can be efficacious in RA by the disruption of B-cell activation and autoantibody production, B-cell synovial migration and ectopic GC formation. Finally, targeting the signal transduction pathways required for proximal BCR signaling has also been found efficacious in early clinical trials in RA. Even so, some B cells inhibit immune responses, these regulatory B cells may play a part in immune regulation in patients and it is unclear what effects B cell depletion strategies have in terms of such B cell subsets. This review discusses current strategies of targeting B-cells as therapeutic candidates in the management of RA. Better insights into the pathogenic role of B-cells provide efficacious opportunities to improve both therapy and prognosis of patients with RA. 相似文献
20.
Celia Barrio-Alonso Alicia Nieto-Valle Elena García-Martínez Alba Gutiérrez-Seijo Verónica Parra-Blanco Iván Márquez-Rodas José Antonio Avilés-Izquierdo Paloma Sánchez-Mateos Rafael Samaniego 《The Journal of pathology》2024,262(4):495-504
During cancer evolution, tumor cells attract and dynamically interact with monocytes/macrophages. To find biomarkers of disease progression in human melanoma, we used unbiased RNA sequencing and secretome analyses of tumor–macrophage co-cultures. Pathway analysis of genes differentially modulated in human macrophages exposed to melanoma cells revealed a general upregulation of inflammatory hallmark gene sets, particularly chemokines. A selective group of chemokines, including CCL8, CCL15, and CCL20, was actively secreted upon melanoma–macrophage co-culture. Because we previously described the role of CCL20 in melanoma, we focused our study on CCL8 and CCL15 and confirmed that in vitro both chemokines contributed to melanoma survival, proliferation, and 3D invasion through CCR1 signaling. In vivo, both chemokines enhanced primary tumor growth, spontaneous lung metastasis, and circulating tumor cell survival and lung colonization in mouse xenograft models. Finally, we explored the clinical significance of CCL8 and CCL15 expression in human skin melanoma, screening a collection of 67 primary melanoma samples, using multicolor fluorescence and quantitative image analysis of chemokine–chemokine receptor content at the single-cell level. Primary skin melanomas displayed high CCR1 expression, but there was no difference in its level of expression between metastatic and nonmetastatic cases. By contrast, comparative analysis of these two clinically divergent groups showed a highly significant difference in the cancer cell content of CCL8 (p = 0.025) and CCL15 (p < 0.0001). Kaplan–Meier curves showed that a high content of CCL8 or CCL15 in cancer cells correlated with shorter disease-free and overall survival (log-rank test, p < 0.001). Our results highlight the role of CCL8 and CCL15, which are highly induced by melanoma–macrophage interactions in biologically aggressive primary melanomas and could be clinically applicable biomarkers for patient profiling. © 2024 The Pathological Society of Great Britain and Ireland. 相似文献