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https://www.readbyqxmd.com/read/29779263/effects-of-porphyromonas-gingivalis-lps-and-lr12-peptide-on-trem-1-expression-by-monocytes
#1
M Dubar, K Carrasco, S Gibot, C Bisson
Periodontal disease involves the activation of host immune response, acting not only as defender of periodontal tissues against bacterial aggression but also as mediator of tissue destruction. Triggering Receptor Expressed on Myeloid cells 1 (TREM-1) is an immune receptor that synergizes with Toll-like receptors in amplifying the inflammatory response mediated by microbial molecules. AIM: To investigate the role of P. gingivalis lipopolysaccharide (LPS) and the effect of LR12, a TREM-1 inhibitory peptide, on the expression of membrane-bound and soluble form of TREM-1 on human primary monocytes, as well as the production of pro-inflammatory cytokines...
May 19, 2018: Journal of Clinical Periodontology
https://www.readbyqxmd.com/read/29779041/the-potential-importance-of-myeloid-derived-suppressor-cells-mdscs-in-the-pathogenesis-of-alzheimer-s-disease
#2
REVIEW
Antero Salminen, Kai Kaarniranta, Anu Kauppinen
The exact cause of Alzheimer's disease (AD) is still unknown, but the deposition of amyloid-β (Aβ) plaques and chronic inflammation indicates that immune disturbances are involved in AD pathogenesis. Recent genetic studies have revealed that many candidate genes are expressed in both microglia and myeloid cells which infiltrate into the AD brains. Invading myeloid cells controls the functions of resident microglia in pathological conditions, such as AD pathology. AD is a neurologic disease with inflammatory component where the immune system is not able to eliminate the perpetrator, while, concurrently, it should prevent neuronal injuries induced by inflammation...
May 19, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29778505/novel-peptide-nanoparticle-biased-antagonist-of-ccr3-blocks-eosinophil-recruitment-and-airway-hyperresponsiveness
#3
Milica Grozdanovic, Kimberly G Laffey, Hazem Abdelkarim, Ben Hitchinson, Anantha Harijith, Hyung-Geon Moon, Gye Young Park, Lee K Rousslang, Joanne C Masterson, Glenn T Furuta, Nadya I Tarasova, Vadim Gaponenko, Steven J Ackerman
BACKGROUND: Chemokine signaling through CCR3 is a key regulatory pathway for eosinophil recruitment into tissues associated with allergic inflammation and asthma. To date, none of the CCR3 antagonists have shown efficacy in clinical trials. One reason may be their unbiased mode of inhibition that prevents receptor internalization, leading to drug tolerance. OBJECTIVE: We sought to develop a novel peptide nanoparticle CCR3 inhibitor (R321) with a biased mode of inhibition that would block G-protein signaling, but enable or promote receptor internalization...
May 17, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29777988/insight-into-structural-requirements-for-selective-and-or-dual-cxcr3-and-cxcr4-allosteric-modulators
#4
Anja Kolarič, Urban Švajger, Tihomir Tomašič, Regine Brox, Theresa Frank, Nikola Minovski, Nuska Tschammer, Marko Anderluh
Based on the previously published pyrazolopyridine-based hit compound for which negative allosteric modulation of both CXCR3 and CXCR4 receptors was disclosed, we designed, synthesized and biologically evaluated a set of novel, not only negative, but also positive allosteric modulators with preserved pyrazolopyridine core. Compound 9e is a dual negative modulator, inhibiting G protein activity of both receptors. For CXCR4 receptor para-substituted aromatic group of compounds distinguishes between negative and positive modulation...
May 11, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29777875/switching-cell-penetrating-and-cxcr4-binding-activities-of-nanoscale-organized-arginine-rich-peptides
#5
Marianna Teixeira de Pinho Favaro, Naroa Serna, Laura Sánchez-García, Rafael Cubarsi, Mónica Roldán, Alejandro Sánchez-Chardi, Ugutz Unzueta, Ramón Mangues, Neus Ferrer-Miralles, Adriano Rodrigues Azzoni, Esther Vázquez, Antonio Villaverde
Arginine-rich protein motifs have been described as potent cell-penetrating peptides (CPPs) but also as rather specific ligands of the cell surface chemokine receptor CXCR4, involved in the infection by the human immunodeficiency virus (HIV). Polyarginines are commonly used to functionalize nanoscale vehicles for gene therapy and drug delivery, aimed to enhance cell penetrability of the therapeutic cargo. However, under which conditions these peptides do act as either unspecific or specific ligands is unknown...
May 16, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29777718/malnutrition-is-associated-with-diminished-baseline-and-mycobacterial-antigen-stimulated-chemokine-responses-in-latent-tuberculosis-infection
#6
Rajamanickam Anuradha, Saravanan Munisankar, Yukthi Bhootra, Nathella Pavan Kumar, Chandrakumar Dolla, Subash Babu
OBJECTIVES: Previous studies have demonstrated a diminution in the baseline and mycobacterial antigen - specific cytokines in low body mass index (LBMI) individuals with latent tuberculosis infection (LTBI). We hypothesized that LBMI might be also associated with alteration in the baseline and antigen - stimulated levels of chemokines in LTBI. METHODS: To test this hypothesis, we examined baseline, TB- antigen and mitogen stimulated levels of chemokines in these individuals and compared them with those with LTBI and normal BMI (NBMI)...
May 16, 2018: Journal of Infection
https://www.readbyqxmd.com/read/29777221/chemokines-and-integrins-independently-tune-actin-flow-and-substrate-friction-during-intranodal-migration-of-t-cells
#7
Miroslav Hons, Aglaja Kopf, Robert Hauschild, Alexander Leithner, Florian Gaertner, Jun Abe, Jörg Renkawitz, Jens V Stein, Michael Sixt
Although much is known about the physiological framework of T cell motility, and numerous rate-limiting molecules have been identified through loss-of-function approaches, an integrated functional concept of T cell motility is lacking. Here, we used in vivo precision morphometry together with analysis of cytoskeletal dynamics in vitro to deconstruct the basic mechanisms of T cell migration within lymphatic organs. We show that the contributions of the integrin LFA-1 and the chemokine receptor CCR7 are complementary rather than positioned in a linear pathway, as they are during leukocyte extravasation from the blood vasculature...
May 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29777028/microrna-302-cluster-downregulates-enterovirus-71-induced-innate-immune-response-by-targeting-kpna2
#8
Nanfang Peng, Xuecheng Yang, Chengliang Zhu, Li Zhou, Haisheng Yu, Mengqi Li, Yong Lin, Xueyu Wang, Qian Li, Yinglong She, Jun Wang, Qian Zhao, Mengji Lu, Ying Zhu, Shi Liu
Enterovirus 71 (EV71) induces significantly elevated levels of cytokines and chemokines, leading to local or systemic inflammation and severe complications. As shown in our previous study, microRNA (miR) 302c regulates influenza A virus-induced IFN expression by targeting NF-κB-inducing kinase. However, little is known about the role of the miR-302 cluster in EV71-mediated proinflammatory responses. In this study, we found that the miR-302 cluster controls EV71-induced cytokine expression. Further studies demonstrated that karyopherin α2 (KPNA2) is a direct target of the miR-302 cluster...
May 18, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29777009/feasibility-of-cxcr4-directed-radioligand-therapy-in-advanced-diffuse-large-b-cell-lymphoma
#9
Constantin Lapa, Heribert Hänscheid, Malte Kircher, Andreas Schirbel, Gerd Wunderlich, Rudolf Werner, Samuel Samnick, Jörg Kotzerke, Hermann Einsele, Andreas Buck, Hans-Jürgen Wester, Götz Ulrich Grigoleit
We have recently reported on our experience with C-X-C-motif chemokine receptor 4- (CXCR4-) directed radioligand therapy (RLT) in multiple myeloma and acute leukemia. Methods: Six patients with heavily pre-treated relapsed diffuse large B cell lymphoma (DLBCL) (3 males, 3 females; aged, 54±8 years) underwent CXCR4-directed RLT in combination with conditioning chemotherapy and allogeneic stem cell transplantation (SCT). In 2 patients, radioimmunotherapy (RIT) targeting CD20 or CD66 was added to enhance anti-lymphoma activity...
May 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29776718/high-urinary-ferritin-reflects-myoglobin-iron-evacuation-in-dmd-patients
#10
Jérémy Rouillon, Thibaud Lefebvre, Jérôme Denard, Vincent Puy, Raed Daher, Jérôme Ausseil, Aleksandar Zocevic, Paul Fogel, Katell Peoc'h, Brenda Wong, Laurent Servais, Thomas Voit, Herve Puy, Zoubida Karim, Fedor Svinartchouk
Duchenne muscular dystrophy (DMD) is an X-linked disease caused by mutations in the dystrophin gene leading to the absence of the normal dystrophin protein. The efforts of many laboratories brought new treatments of DMD to the reality, but ongoing and forthcoming clinical trials suffer from absence of valuable biomarkers permitting to follow the outcome of the treatment day by day and to adjust the treatment if needed. In the present study the levels of 128 urinary proteins including growth factors, cytokines and chemokines were compared in urine of DMD patients and age related control subjects by antibody array approach...
March 20, 2018: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/29776413/the-cxcr4-antagonist-plerixafor-amd3100-promotes-proliferation-of-ewing-sarcoma-cell-lines-in-vitro-and-activates-receptor-tyrosine-kinase-signaling
#11
Philipp Berning, Christiane Schaefer, Dagmar Clemens, Eberhard Korsching, Uta Dirksen, Jenny Potratz
BACKGROUND: The CXCR4 receptor antagonist plerixafor (AMD3100) is raising interest as an anti-cancer agent that disrupts the CXCL12-CXCR4 chemokine - receptor interaction between neoplastic cells and their microenvironment in tumor progression and metastasis. Here, we investigated plerixafor for anti-cancer activity in Ewing sarcoma, a rare and aggressive cancer of bone and soft tissues. METHODS: We used a variety of methods such as cell viability and migration assays, flow cytometry, phospho-tyrosine arrays and western blotting to determine plerixafor effects on five characterized Ewing sarcoma cell lines and a low-passage culture in vitro...
May 18, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29775920/il-33-stimulates-expression-of-the-gpr84-ex33-fatty-acid-receptor-gene-and-of-cytokine-and-chemokine-genes-in-human-adipocytes
#12
Mohamed S Zaibi, Małgorzata A Kępczyńska, Parvathy Harikumar, Suliman Y Alomar, Paul Trayhurn
Expression of GPCR fatty acid sensor/receptor genes in adipocytes is modulated by inflammatory mediators, particularly IL-1β. In this study we examined whether the IL-1 gene superfamily member, IL-33, also regulates expression of the fatty acid receptor genes in adipocytes. Human fat cells, differentiated from preadipocytes, were incubated with IL-33 at three different dose levels for 3 or 24 h and mRNA measured by qPCR. Treatment with IL-33 induced a dose-dependent increase in GPR84 mRNA at 3 h, the level with the highest dose being 13...
May 15, 2018: Cytokine
https://www.readbyqxmd.com/read/29775758/lncrna-prncr1-regulates-osteogenic-differentiation-in-osteolysis-after-hip-replacement-by-targeting-mir-211-5p
#13
Zong-Ming Gong, Zhen-Yu Tang, Xiao-Liang Sun
BACKGROUND: Osteogenic differentiation and osteolysis after hip replacement are both associated with bone metabolism. Interaction between lncRNA PRNCR1 and miR-211-5p was analyzed to illuminate their roles in osteogenic differentiation and osteolysis. METHODS: The expression of PRNCR1, miR-211-5p and C-X-C chemokine receptor-4 (CXCR4) protein in tissues and mesenchymal stem cells (MSCs) were determined by qRT-PCR and Western blot, separately. The osteogenic differentiation was assessed by ALP activity detection and ARS staining...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29775613/suppression-of-nlrp3-inflammasome-attenuates-stress-induced-depression-like-behavior-in-nlgn3-deficient-mice
#14
Ze-Qun Li, Zhi-Yuan Yan, Bo-Jun Lan, Yi-Qun Dong, Ye Xiong
Depression, regulated by central nervous system (CNS), is a significant inflammatory disorder. Neuroligin3 (NLGN3) has been implicated in brain functions. In the study, a chronic unpredictable mild stress (CUMS) model in wild type (WT) or NLGN3-knockout (KO) mice was established to explore the role of NLGN3 in regulating depression and to reveal the underlying molecular mechanism. The results indicated that NLGN3-knockout markedly reversed the loss of body weight, the reduction of sucrose consumption, the decrease of immobile time in the forced swimming tests (FST) and tail suspension tests (TST) induced by CUMS paradigm...
May 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29775225/cytokines-and-chemokines-differentially-regulate-innate-immune-cell-trafficking-during-post-kala-azar-dermal-leishmaniasis
#15
Ashish K Singh, Vidya N R Das, Ajay Amit, Manas R Dikhit, Vijaya Mahantesh, Shubhankar K Singh, Shyam Naryan, Krishna Pandey, Pradeep Das, Neena Verma, Sanjiva Bimal
Post kala-azar dermal leishmaniasis (PKDL) is often considered to be the anthroponotic reservoir of visceral leishmaniasis (VL) in India. A better understanding of the host immune-response in dermal lesions of PKDL patients is therefore of utmost significance to minimize such patients and to restrict VL transmission. Although the innate immune response is known to play an important role in parasite clearance from dermal lesions, the actual contribution of innate cells to the pathogenicity of PKDL is poorly understood...
May 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29775223/curcumin-down-regulates-il-17a-mediated-p53-fibrinolytic-system-in-bleomycin-induced-acute-lung-injury-in-vivo
#16
Mahesh M Gouda, Yashodhar P Bhandary
Bleomycin (BLM) induced cellular damage causes inflammation in the alveolar compartment and impairment of fibrinolytic system leads to alveolar epithelial cell apoptosis. Here, we describe novel inflammatory pathway associated with p53-fibrinolytic system and apoptosis of alveolar epithelial cells and pharmacological efficiency of curcumin against this action. In the present study we used C57BL/6 mice. The specific dose and time interval of curcumin were analyzed to assess the intervention. Experiments were designed to investigate the IL-17A mediated modulation in the alveolar epithelial cell apoptosis and injury...
May 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29774022/acute-zika-virus-infection-in-an-endemic-area-shows-modest-proinflammatory-systemic-immunoactivation-and-cytokine-symptom-associations
#17
Jéssica Barletto de Sousa Barros, Paulo Alex Neves da Silva, Rosemary de Carvalho Rocha Koga, Patrícia Gonzalez-Dias, José Rodrigues Carmo Filho, Patrícia Resende Alo Nagib, Verônica Coelho, Helder I Nakaya, Simone Gonçalves Fonseca, Irmtraut Araci Hoffmann Pfrimer
An early immune response to Zika virus (ZIKV) infection may determine its clinical manifestation and outcome, including neurological effects. However, low-grade and transient viremia limits the prompt diagnosis of acute ZIKV infection. We have investigated the plasma cytokine, chemokine, and growth factor profiles of 36 individuals from an endemic area displaying different symptoms such as exanthema, headache, myalgia, arthralgia, fever, hyperemia, swelling, itching, and nausea during early-phase infection...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29773890/intraperitoneal-administration-of-the-anti-il-23-antibody-prevents-the-establishment-of-intestinal-nematodes-in-mice
#18
M Gomez-Samblas, D Bernal, A Bolado-Ortiz, S Vilchez, F Bolás-Fernández, A M Espino, M Trelis, A Osuna
Previous studies have established that an increased Th-9 response creates a hostile environment for nematode parasites. Given that IL-23, a cytokine required for maintenance of the IL-17-secreting phenotype, has inhibitory effects on IL-9 production, we hypothesized that reducing circulating IL-23 by treatment with anti-IL-23 antibodies would reduce the establishment and development of parasitic intestinal nematodes. In this study, we show that animals treated with anti-IL-23 monoclonal antibodies showed a drastic reduction in the number of mouse pinworms (Aspiculuris tetraptera) recovered from the intestine (p < 0...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773802/cd4-t-cells-are-activated-in-regional-lymph-nodes-and-migrate-to-skin-to-initiate-lymphedema
#19
Gabriela D García Nores, Catherine L Ly, Daniel A Cuzzone, Raghu P Kataru, Geoffrey E Hespe, Jeremy S Torrisi, Jung Ju Huang, Jason C Gardenier, Ira L Savetsky, Matthew D Nitti, Jessie Z Yu, Sonia Rehal, Babak J Mehrara
T cell-mediated responses have been implicated in the development of fibrosis, impaired lymphangiogenesis, and lymphatic dysfunction in secondary lymphedema. Here we show that CD4+ T cells are necessary for lymphedema pathogenesis by utilizing adoptive transfer techniques in CD4 knockout mice that have undergone tail skin and lymphatic excision or popliteal lymph node dissection. We also demonstrate that T cell activation following lymphatic injury occurs in regional skin-draining lymph nodes after interaction with antigen-presenting cells such as dendritic cells...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29772686/inhibition-of-the-ccl5-ccr5-axis-against-the-progression-of-gastric-cancer
#20
REVIEW
Donatella Aldinucci, Naike Casagrande
Despite the progress made in molecular and clinical research, patients with advanced-stage gastric cancer (GC) have a bad prognosis and very low survival rates. Furthermore, it is challenging to find the complex molecular mechanisms that are involved in the development of GC, its progression, and its resistance to therapy. The interactions of chemokines, also known as chemotactic cytokines, with their receptors regulate immune and inflammatory responses. However, updated research demonstrates that cancer cells subvert the normal chemokine role, transforming them into fundamental constituents of the tumor microenvironment (TME) with tumor-promoting effects...
May 16, 2018: International Journal of Molecular Sciences
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