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Anti- cytokine therapies

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https://www.readbyqxmd.com/read/28229922/mandevilla-longiflora-desf-pichon-improves-airway-inflammation-in-a-murine-model-of-allergic-asthma
#1
Danielle Ayr Tavares de Almeida, Suellen Iara Guirra Rosa, Thais Campos Dias da Cruz, Eduarda Pavan, Amílcar Sabino Damazo, Ilsamar Mendes Soares, Sérgio Donizeti Ascêncio, Antonio Macho, Domingos Tabajara de Oliveira Martins
ETHNOPHARMACOLOGICAL RELEVANCE: Mandevilla longiflora, popularly known as "velame" in central Brazil, is a subshrub and widely distributed in South America. Its xylopodium is used in the form of a decoction or infusion to treat inflammation and other ailments. AIM OF THE STUDY: This study aimed to evaluate the anti-inflammatory potential of M. longiflora in an in vivo model of ovalbumin-induced immediate hypersensitivity, identifying its effects on leukocyte infiltration, IgE and LTB4 levels, and Th2 cytokine production...
February 13, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28224701/pathogenic-role-of-anti-srp-and-anti-hmgcr-antibodies-in-necrotizing-myopathies-myofiber-atrophy-and-impairment-of-muscle-regeneration-in-necrotizing-autoimmune-myopathies
#2
Louiza Arouche-Delaperche, Yves Allenbach, Damien Amelin, Corinna Preusse, Vincent Mouly, Wladimir Mauhin, Gaelle Dzangue Tchoupou, Laurent Drouot, Olivier Boyer, Werner Stenzel, Gillian Butler-Browne, Olivier Benveniste
OBJECTIVE: Immune mediated necrotizing myopathies (IMNM) may be associated with either anti-SRP or anti-HMGCR antibodies (Abs) and the titer of these Abs is correlated with the disease activity. We investigated if anti-SRP and anti-HMGCR Abs could be involved in muscle damages. METHODS: Muscle biopsies of patients were analyzed for atrophy and regeneration, by measuring the fibers size and by performing immunostaining of neonatal myosin heavy chain. To further understand the role of the Abs in the pathology, we performed muscle cell co-culture with the Abs...
February 22, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28223983/b-cell-homeostasis-and-functional-properties-are-altered-in-an-hypochlorous-acid-induced-murine-model-of-systemic-sclerosis
#3
Sébastien Sanges, Manel Jendoubi, Niloufar Kavian, Carine Hauspie, Silvia Speca, Jean-Charles Crave, Thomas Guerrier, Guillaume Lefèvre, Vincent Sobanski, Ariel Savina, Eric Hachulla, Pierre-Yves Hatron, Myriam Labalette, Frédéric Batteux, Sylvain Dubucquoi, David Launay
INTRODUCTION: During systemic sclerosis (SSc), peripheral B cells display alterations in subset homeostasis and functional properties and are a promising therapeutic target. However, there is only few data regarding whether these anomalies are accurately reproduced in animal models of SSc. OBJECTIVE: In this work, we assessed the B cell homeostasis modifications in an experimental model of SSc [hypochlorous acid (HOCl)-induced mouse], both at a phenotypic and functional level, during the course of the disease...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28223693/single-cd28-stimulation-induces-stable-and-polyclonal-expansion-of-human-regulatory-t-cells
#4
Xuehui He, Ruben L Smeets, Esther van Rijssen, Annemieke M H Boots, Irma Joosten, Hans J P M Koenen
CD4+FOXP3+ Treg are essential for immune tolerance. Phase-1 clinical trials of Treg-therapy to treat graft-versus-host-disease reported safety and potential therapeutic efficacy. Treg-based trials have started in organ-transplant patients. However, efficient ex vivo expansion of a stable Treg population remains a challenge and exploring novel ways for Treg expansion is a pre-requisite for successful immunotherapy. Based on the recent finding that CD28-signaling is crucial for survival and proliferation of mouse Treg, we studied single-CD28 stimulation of human Treg, without T cell receptor stimulation...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28219887/disruption-of-pathogenic-cellular-networks-by-il-21-blockade-leads-to-disease-amelioration-in-murine-lupus
#5
Jin-Young Choi, Abhinav Seth, Michael Kashgarian, Sonia Terrillon, Emma Fung, Lili Huang, Li Chun Wang, Joe Craft
Systemic lupus erythematosus (lupus) is characterized by autoantibody-mediated organ injury. Follicular Th (Tfh) cells orchestrate physiological germinal center (GC) B cell responses, whereas in lupus they promote aberrant GC responses with autoreactive memory B cell development and plasma cell-derived autoantibody production. IL-21, a Tfh cell-derived cytokine, provides instructional cues for GC B cell maturation, with disruption of IL-21 signaling representing a potential therapeutic strategy for autoantibody-driven diseases such as systemic lupus erythematosus...
February 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28216374/yin-yang-effect-of-tumor-infiltrating-b-cells-in-breast-cancer-from-mechanism-to-immunotherapy
#6
Zhigang Zhang, Ying Zhu, Zhen Wang, Ting Zhang, Pin Wu, Jian Huang
Breast cancer cells secrete chemokines, such as CXCL13, and antigens or express high endothelial venules, attracting B cells to infiltrate into the tumor microenvironment and play a "yin-yang" effect. They not only enhance the anti-tumor immune effect via secreting antibodies and influencing the Fas/FasL, CXCR4/CXCL12 and perforin pathways but they also promote the tumor to form a suppressive milieu by producing immunomodulatory factors and cytokines or using cell-to-cell education to induce the generation of Tregs or myeloid-derived suppressor cells (MDSCs)...
February 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28215362/efficacy-and-safety-of-sirukumab-in-patients-with-active-rheumatoid-arthritis-refractory-to-anti-tnf-therapy-sirround-t-a-randomised-double-blind-placebo-controlled-parallel-group-multinational-phase-3-study
#7
Daniel Aletaha, Clifton O Bingham, Yoshiya Tanaka, Prasheen Agarwal, Regina Kurrasch, Paul P Tak, Sharon Popik
BACKGROUND: Sirukumab, a human monoclonal antibody that selectively binds to the interleukin-6 cytokine with high affinity, is under development for the treatment of rheumatoid arthritis and other diseases. We aimed to assess the efficacy and safety of sirukumab for rheumatoid arthritis in a phase 3 study (SIRROUND-T). METHODS: We did a randomised, double-blind, placebo-controlled, parallel-group, multicentre study at 183 hospitals and private rheumatology clinics in 20 countries (Argentina, Australia, Austria, Belgium, Canada, France, Germany, Italy, Japan, Lithuania, Mexico, Netherlands, Poland, Portugal, Russia, South Korea, Spain, Taiwan, UK, and USA)...
February 15, 2017: Lancet
https://www.readbyqxmd.com/read/28214071/lipocalin-2-a-master-mediator-of-intestinal-and-metabolic-inflammation
#8
REVIEW
Alexander R Moschen, Timon E Adolph, Romana R Gerner, Verena Wieser, Herbert Tilg
Lipocalin-2 (LCN2), also known as neutrophil gelatinase-associated lipocalin (NGAL), is released by various cell types and is an attractive biomarker of inflammation, ischemia, infection, and kidney damage. Both intestinal and metabolic inflammation, as observed in obesity and related disorders, are associated with increased LCN2 synthesis. While LCN2 in the intestinal tract regulates the composition of the gut microbiota and shows anti-inflammatory activities, it also exhibits proinflammatory activities in other experimental settings...
February 14, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28212280/biofilm-formation-and-immunomodulatory-activity-of-proteus-mirabilis-clinically-isolated-strains
#9
Alessandra Fusco, Lorena Coretti, Vittoria Savio, Elisabetta Buommino, Francesca Lembo, Giovanna Donnarumma
Urinary tract infections (UTIs) and catheter-associated UTIs (CAUTIs) are the principal hospital-acquired infections. Proteus mirabilis is characterized by several virulence factors able to promote adhesion and biofilm formation and ameliorate the colonization of urinary tract and the formation of crystalline biofilms on the abiotic surface of the urinary catheters. Since, to date, the role of P. mirabilis in the etiopathogenesis of different types of urinary tract infections is not well established, in this study we sought to characterize two different clinically isolated strains of P...
February 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28211040/anti-cd3-treatment-upregulates-pd-1-expression-on-activated-effector-t-cells-and-severely-impairs-their-inflammatory-capacity
#10
Maja Wallberg, Asha Recino, Jenny Phillips, Duncan Howie, Margaux Vienne, Christopher Paluch, Miyuki Azuma, F Susan Wong, Herman Waldmann, Anne Cooke
T cells play a key role in the pathogenesis of type 1 diabetes, and targeting the CD3 component of the TCR complex provides one therapeutic approach. Anti-CD3 treatment can reverse overt disease in spontaneously diabetic non-obese diabetic mice, an effect proposed to, at least in part, be caused by a selective depletion of pathogenic cells. We have used a transfer model to further investigate the effects of anti-CD3 treatment on green fluorescent protein (GFP)(+) islet-specific effector T cells in vivo. The GFP expression allowed us to isolate the known effectors at different time points during treatment to assess cell presence in various organs as well as gene expression and cytokine production...
February 17, 2017: Immunology
https://www.readbyqxmd.com/read/28208594/immunomodulatory-and-anti-ibdv-activities-of-the-polysaccharide-aex-from-coccomyxa-gloeobotrydiformis
#11
Qiang Guo, Qiang Shao, Wenping Xu, Lei Rui, Ryo Sumi, Fumio Eguchi, Zandong Li
A number of polysaccharides have been reported to show immunomodulatory and antiviral activities against various animal viruses. AEX is a polysaccharide extracted from the green algae, Coccomyxa gloeobotrydiformis. The aim of this study was to examine the function of AEX in regulating the immune response in chickens and its capacity to inhibit the infectious bursal disease virus (IBDV), to gain an understanding of its immunomodulatory and antiviral ability. Here, preliminary immunological tests in vitro showed that the polysaccharide AEX can activate the chicken peripheral blood molecular cells' (PBMCs) response by inducing the production of cytokines and NO, promote extracellular antigen presentation but negatively regulate intracellular antigen presentation in chicken splenic lymphocytes, and promote the proliferation of splenic lymphocytes and DT40 cells...
February 10, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28206989/il-4-mediated-by-hsv-vector-suppresses-morphine-withdrawal-response-through-decreasing-tnf%C3%AE-nr2b-and-pc-ebp%C3%AE-in-the-periaqueductal-gray-in-rats
#12
H Yi, T Iida, S Liu, D Ikegami, Q Liu, A Iida, D A Lubarsky, S Hao
Chronic opiates induce the development of physical dependence. Opioid physical dependence characterized by withdrawal symptoms, may have very long-lasting effects on the motivation for reward, including the incubation of cue-induced drug-seeking behavior. Elucidation of the mechanisms involved in physical dependence is crucial to developing more effective treatment strategies for opioid dependence. Chronic morphine induces production of proinflammatory cytokines in regional-specific sites of the brain. Interleukin-4 (IL-4) is a prototypical anti-inflammatory cytokine that globally suppresses proinflammatory cytokines...
February 16, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28206713/effect-of-heme-oxygenase-1-transduced-bone-marrow-mesenchymal-stem-cells-on-damaged-intestinal-epithelial-cells-in-vitro
#13
Yi Cao, Ben-Juan Wu, Wei-Ping Zheng, Ming-Li Yin, Tao Liu, Hong-Li Song
In this study we explored the effects of mesenchymal stem cells (MSCs) from bone marrow overexpressing heme oxygenase-1 (HO-1) on the damaged human intestinal epithelial barrier in vitro. Rat MSCs were isolated from bone marrow and transduced with rat HO-1 recombinant adenovirus (HO-MSCs) for stable expression of HO-1. Colorectal adenocarinoma 2 (Caco2) cells were treated with tumor necrosis factor-α (TNF-α) to establish a damaged colon epithelial model. Damaged Caco2 were cocultured with MSCs, Ad-MSCs, Ad-HO + MSCs or HO-MSCs mRNA and protein expression of Zona occludens-1 (ZO-1) and human HO-1, and the release of cytokines were measured...
February 16, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28202530/therapeutic-potential-of-bacteria-against-solid-tumors
#14
Haralampos Hatzikirou, Juan Carlos Lopez Alfonso, Sara Leschner, Siegfried Weiss, Michael Meyer-Hermann
Intentional bacterial infections can produce efficacious anti-tumor responses in mice, rats, dogs and humans. However, low overall success rates and intense side-effects prevent such approaches from being employed clinically. In this work, we titered bacteria and/or the pro-inflammatory cytokine TNF-α in a set of established murine models of cancer. To interpret the experiments conducted, we considered and calibrated a tumor-effector cell recruitment model under the influence of functional tumor-associated vasculature...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28202394/platelet-rich-plasma-prp-induces-chondroprotection-via-increasing-autophagy-anti-inflammatory-markers-and-decreasing-apoptosis-in-human-osteoarthritic-cartilage
#15
Mayssam Moussa, Daniel Lajeunesse, George Hilal, Oula El Atat, Gaby Haykal, Rim Serhal, Antonio Chalhoub, Charbel Khalil, Nada Alaaeddine
OBJECTIVES: Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration...
February 13, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28199785/assessment-of-tocilizumab-anti-il-6-receptor-monoclonal-as-a-potential-treatment-for-chronic-antibody-mediated-rejection-and-transplant-glomerulopathy-in-hla-sensitized-renal-allograft-recipients
#16
Jua Choi, Olivier Aubert, Ashley Vo, Alexandre Loupy, Mark Haas, Dechu Puliyanda, Irene Kim, Sabrina Louie, Alexis Kang, Alice Peng, Joe Kahwaji, Nancy Reinsmoen, Mieko Toyoda, Stanley C Jordan
Extending the functional integrity of renal allografts is the primary goal of transplant medicine. Development of donor-specific antibodies (DSAs) post-transplant leads to chronic active antibody-mediated rejection (cABMR) and transplant glomerulopathy (TG), resulting in the majority of graft losses in the U.S. This reduces the quality & length of life for patients and increases cost. There are no approved treatments for cABMR. Evidence suggests the pro-inflammatory cytokine interleukin 6 (IL-6) may play an important role in DSA generation and cABMR...
February 15, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28197626/kdm6a-and-kdm6b-altered-expression-in-malignant-pleural-mesothelioma
#17
Sian Cregan, Maeve Breslin, Gerard Roche, Sigrid Wennstedt, Lauren MacDonagh, Cinaria Albadri, Yun Gao, Kenneth J O'Byrne, Sinead Cuffe, Stephen P Finn, Steven G Gray
Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura primarily associated with prior exposure to asbestos. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients, however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. Inflammation is thought to be a key element in the pathogenesis of MPM, and recently Kdm6 family members (Kdm6a and Kdm6b) have been identified as playing important roles in inflammatory processes...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28197389/adaptive-resistance-to-anti-pd1-therapy-by-tim-3-upregulation-is-mediated-by-the-pi3k-akt-pathway-in-head-and-neck-cancer
#18
Gulidanna Shayan, Raghvendra Srivastava, Jing Li, Nicole Schmitt, Lawrence P Kane, Robert L Ferris
Programmed Death 1 (PD-1) and T cell Ig and mucin domain-3 protein (Tim-3) are immune checkpoint receptors that are expressed on tumor-infiltrating lymphocytes (TIL) in tumor-bearing mice and humans. As anti-PD-1 single agent response rates are only <20% in head and neck squamous cell carcinoma (HNSCC) patients, it is important to understand how multiple inhibitory checkpoint receptors maintain suppressed cellular immunity. One such receptor, Tim-3, activates downstream proliferative pathways through Akt/S6, and is highly expressed in dysfunctional TIL...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28195065/effect-of-econazole-and-benzydamine-on-sensory-neurons-in-culture
#19
S Mathivanan, R de la Torre-Martinez, C Wolf, G Mangano, L Polenzani, C Milanese, A Ferrer-Montiel
Econazole is an anti-mycotic agent widely used for the treatment of cutaneous fungal infections, and for the therapy of vaginal candidiasis. Topical application of this azole is generally safe, although some patients have complained of mild burning sensation/cutaneous irritation and itching, especially when administered intravaginally. The underlying mechanisms responsible of these adverse effects are poorly understood, though they suggest excitation of cutaneous nociceptor terminals. We report that exposure of primary cultures of rat nociceptors to econazole augments neuronal excitability...
December 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28191667/metastatic-recurrence-of-17-years-relapse-free-melanoma-during-anti-tnfa-therapy
#20
Ioana Cosgarea, Andreas Körber, Dorothee Dill, Dirk Schadendorf, Selma Ugurel
Tumor-necrosis-factor-alpha (TNFa) is an innate cytokine involved in regulating inflammation, immunity, tumorigenesis, and apoptosis. TNFa inhibitors became a powerful tool in the treatment of auto-immune inflammatory diseases such as Crohn's disease, ulcerative colitis, rheumatoid arthritis and psoriasis. Known side effects of TNFa inhibitors range from infections to malignancies [1]. We report a male patient who was in 1998 at age 36 diagnosed with amelanotic melanoma of the leg, Breslow thickness 11.0 mm, no ulceration...
February 13, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
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