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https://www.readbyqxmd.com/read/28620197/interleukin-28b-dampens-airway-inflammation-through-up-regulation-of-natural-killer-cell-derived-ifn-%C3%AE
#1
Bailing Yan, Feng Chen, Lijun Xu, Yanshi Wang, Xuefu Wang
Interleukin-28A (IL-28A) modulates CD11c+ dendritic cell (DC) function and promotes type 1T helper (Th1) differentiation, thus suppressing allergic airway diseases. However, the function of the IL-28A isoform IL-28B in these diseases remains largely unknown. In this study, we revealed a novel role of IL-28B in inducing type 1 immunity and protecting against ovalbumin (OVA)-induced allergic asthma in mice. IL-28B overexpression in wild-type mice promoted natural killer (NK) cell polarization in the lung, leading to the increased number of interferon (IFN)-γ-producing NK1 cells as well as Th1 differentiation...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28606851/cardiorespiratory-action-of-opioid-tachykinin-agonist-peptide-hybrid-in-anaesthetized-rats-transduction-pathways
#2
Piotr Wojciechowski, Małgorzata Szereda-Przestaszewska, Andrzej Wojciech Lipkowski
AWL3106 composed of opioid (dermorphin) and tachykinin (substance P7-11) pharmacophores is a new compound with high analgesic potency and markedly reduced ability to induce tolerance and dependence. The present study aimed to determine the respiratory and cardiovascular responses evoked by this peptide in urethane-chloralose anaesthetized, spontaneously breathing rats in the presence or absence of vagal connection. Intravenous injection of AWL3106 at a dose of 0.3μmol/kg in intact rats resulted in apnoea lasting 5...
June 9, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28530714/cd8%C3%AE-%C3%AE-intraepithelial-lymphocytes-arise-from-two-main-thymic-precursors
#3
Roland Ruscher, Rebecca L Kummer, You Jeong Lee, Stephen C Jameson, Kristin A Hogquist
TCRαβ(+)CD4(-)CD8α(+)CD8β(-) intestinal intraepithelial lymphocytes (CD8αα IELs) are an abundant population of thymus-derived T cells that protect the gut barrier surface. We sought to better define the thymic IEL precursor (IELp) through analysis of its maturation, localization and emigration. We defined two precursor populations among TCRβ(+)CD4(-)CD8(-) thymocytes by dependence on the kinase TAK1 and rigorous lineage-exclusion criteria. Those IELp populations included a nascent PD-1(+) population and a T-bet(+) population that accumulated with age...
July 2017: Nature Immunology
https://www.readbyqxmd.com/read/28515228/nk1-1-cells-promote-sustained-tissue-injury-and-inflammation-after-trauma-with-hemorrhagic-shock
#4
Shuhua Chen, Rosemary A Hoffman, Melanie Scott, Joanna Manson, Patricia Loughran, Mostafa Ramadan, Anthony J Demetris, Timothy R Billiar
Various cell populations expressing NK1.1 contribute to innate host defense and systemic inflammatory responses, but their role in hemorrhagic shock and trauma remains uncertain. NK1.1(+) cells were depleted by i.p. administration of anti-NK1.1 (or isotype control) on two consecutive days, followed by hemorrhagic shock with resuscitation and peripheral tissue trauma (HS/T). The plasma levels of IL-6, MCP-1, alanine transaminase (ALT), and aspartate aminotransferase (AST) were measured at 6 and 24 h. Histology in liver and gut were examined at 6 and 24 h...
May 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28501575/the-anti-asthmatic-drug-pranlukast-suppresses-the-delayed-phase-vomiting-and-reverses-intracellular-indices-of-emesis-evoked-by-cisplatin-in-the-least-shrew-cryptotis-parva
#5
Nissar A Darmani, Seetha Chebolu, Weixia Zhong, William D Kim, Matthew Narlesky, Joia Adams, Fanglong Dong
The introduction of second generation serotonin 5-HT3 receptor (5-HT3) antagonist palonosetron combined with long-acting substance P neurokinin NK1 receptor (NK1) antagonists (e.g. netupitant) has substantially improved antiemetic therapy against early- and delayed-phases of emesis caused by highly emetogenic chemotherapeutics such as cisplatin. However, the improved efficacy comes at a cost that many patients cannot afford. We introduce a new class of antiemetic, the antiasthmatic leukotriene CysLT1 receptor antagonist pranlukast for the suppression of cisplatin-evoked vomiting...
May 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28496413/cholera-toxin-induces-sustained-hyperexcitability-in-myenteric-but-not-submucosal-ah-neurons-in-guinea-pig-jejunum
#6
Katerina Koussoulas, Rachel M Gwynne, Jaime P P Foong, Joel C Bornstein
Background and Aims: Cholera toxin (CT)-induced hypersecretion requires activation of secretomotor pathways in the enteric nervous system (ENS). AH neurons, which have been identified as a population of intrinsic sensory neurons (ISNs), are a source of excitatory input to the secretomotor pathways. We therefore examined effects of CT in the intestinal lumen on myenteric and submucosal AH neurons. Methods: Isolated segments of guinea pig jejunum were incubated for 90 min with saline plus CT (12.5 μg/ml) or CT + neurotransmitter antagonist, or CT + tetrodotoxin (TTX) in their lumen...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28493529/pain-in-knee-osteoarthritis-is-associated-with-variation-in-the-neurokinin-1-substance-p-receptor-tacr1-gene
#7
S C Warner, D A Walsh, L L Laslett, R A Maciewicz, A Soni, D J Hart, W Zhang, K R Muir, E M Dennison, P Leaverton, E Rampersaud, C Cooper, T D Spector, F M Cicuttini, N K Arden, G Jones, M Doherty, A M Valdes
BACKGROUND: Substance P (SP) is a pain- and inflammation-related neuropeptide which preferentially binds to the neurokinin receptor 1 (NK1 ). SP and NK1 receptors have been implicated in joint pain, inflammation and damage in animal models and human studies of osteoarthritis (OA). The aim of this study was to test if genetic variation at the neurokinin 1 receptor gene (TACR1) is associated with pain in individuals with radiographic knee OA. METHODS: Participants from the Genetics of OA and Lifestyle study were used for the discovery group (n = 1615)...
May 11, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28485408/genetic-and-pharmacological-antagonism-of-nk1-receptor-prevents-opiate-abuse-potential
#8
A J Sandweiss, M I McIntosh, A Moutal, R Davidson-Knapp, J Hu, A K Giri, T Yamamoto, V J Hruby, R Khanna, T M Largent-Milnes, T W Vanderah
Development of an efficacious, non-addicting analgesic has been challenging. Discovery of novel mechanisms underlying addiction may present a solution. Here we target the neurokinin system, which is involved in both pain and addiction. Morphine exerts its rewarding actions, at least in part, by inhibiting GABAergic input onto substance P (SP) neurons in the ventral tegmental area (VTA), subsequently increasing SP release onto dopaminergic neurons. Genome editing of the neurokinin 1 receptor (NK1R) in the VTA renders morphine non-rewarding...
May 9, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28482051/biomarkers-of-chronic-acrolein-inhalation-exposure-in-mice-implications-for-tobacco-product-induced-toxicity
#9
Daniel J Conklin, Marina V Malovichko, Iris Zeller, Trinath P Das, Tatiana V Krivokhizhina, Blake H Lynch, Pawel Lorkiewicz, Abhinav Agarwal, Nalinie Wickramasinghe, Petra Haberzettl, Srinivas D Sithu, Jasmit Shah, Timothy E O'Toole, Shesh N Rai, Aruni Bhatnagar, Sanjay Srivastava
Exposure to tobacco smoke, which contains several harmful and potentially harmful constituents such as acrolein increases cardiovascular disease (CVD) risk. Although high acrolein levels induce pervasive cardiovascular injury, the effects of low-level exposure remain unknown and sensitive biomarkers of acrolein toxicity have not been identified. Identification of such biomarkers is essential to assess the toxicity of acrolein present at low levels in the ambient air or in new tobacco products such as e-cigarettes...
May 8, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28472227/cortical-nnos-nk1-receptor-neurons-are-regulated-by-cholinergic-projections-from-the-basal-forebrain
#10
Rhîannan H Williams, Jacqueline Vazquez-DeRose, Alexia M Thomas, Juliette Piquet, Bruno Cauli, Thomas S Kilduff
Cholinergic (ACh) basal forebrain (BF) neurons are active during wakefulness and rapid eye movement (REM) sleep and are involved in sleep homeostasis. We have previously shown in adult animals that cortical neurons that express neuronal nitric oxide synthase (nNOS) and the receptor for Substance P (NK1R) are activated during non-REM (NREM) sleep in proportion to homeostatic sleep drive. Here, we show that BF neurons modulate cortical nNOS/NK1R cells. In vitro optogenetic stimulation of BF terminals both activated and inhibited nNOS/NK1R neurons...
May 2, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28464353/neurokinin-1-receptor-blocker-cp-99%C3%A2-994-improved-emesis-induced-by-cisplatin-via-regulating-the-activity-of-gastric-distention-responsive-neurons-in-the-dorsal-motor-nucleus-of-vagus-and-enhancing-gastric-motility-in-rats
#11
X Sun, L Xu, F Guo, W Luo, S Gao, X Luan
BACKGROUND: Nowadays, chemotherapy induced nausea and vomiting (CINV) is still common in patients with cancer. It was reported that substance P mediated CINV via neurokinin-1 (NK1 ) receptor and antagonists of NK1 receptor has been proved useful for treating CINV but the mechanism are not fully understood. This study aimed to examine the role of NK1 receptor blocker, CP-99 994, when administrated into dorsal motor nucleus of vagus (DMNV), on the cisplatin-induced emesis in rats and the possible mechanism...
May 2, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28447301/management-of-chemotherapy-induced-nausea-and-vomiting-in-pediatric-patients
#12
REVIEW
Rudolph M Navari
Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life and is perceived by patients as a major adverse effect of the treatment. This review summarizes the safety and efficacy of current antiemetic agents for the prevention of CINV in children. Information on antiemetic prophylaxis for CINV in children was obtained from a literature review of current peer-reviewed articles and recent international guidelines. The literature review and the international antiemetic guidelines provide recommendations for use of specific antiemetics in children based on the emetogenicity of the chemotherapy...
June 2017: Paediatric Drugs
https://www.readbyqxmd.com/read/28423730/the-sclttaxbcr-abl-transgenic-mouse-model-closely-reflects-the-differential-effects-of-dasatinib-on-normal-and-malignant-hematopoiesis-in-chronic-phase-cml-patients
#13
Claudia Schubert, Nicolas Chatain, Till Braunschweig, Mirle Schemionek, Kristina Feldberg, Melanie Hoffmann, Olli Dufva, Satu Mustjoki, Tim H Brümmendorf, Steffen Koschmieder
The second generation tyrosine kinase inhibitor (TKI) dasatinib is a clinically approved drug for chronic myeloid leukemia (CML) as well as Ph+ acute lymphoblastic leukemia. In addition to its antileukemic effects, dasatinib was shown to impact on normal hematopoiesis and cells of the immune system.Due to the fact that the murine in vivo studies so far have not been performed in a chronic-phase CML model under steady-state conditions, our aim was to study the hematopoietic effects of dasatinib (20 mg/kg p.o...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404628/simultaneous-detection-of-decidual-th1-th2-and-nk1-nk2-immunophenotyping-in-unknown-recurrent-miscarriage-using-8-color-flow-cytometry-with-fsc-vt-extended-strategy
#14
Peng Dong, Xi Wen, Jia Liu, Cui-Yan Yan, Jing Yuan, Lan-Rong Luo, Qiao-Fei Hu, Jian Li
Th1/Th2 imbalance is considered as a mechanism for recurrent miscarriage. The NK1/NK2 paradigm is hypothesised to play an important role in pregnancy. However, few results showed simultaneous changes of these subsets in vivo in decidual tissues. The present study aimed to detect the decidual mononuclear cells (dMo), and the Th1/Th2, and NK1/NK2 paradigm simultaneously using multiparametric flow cytometry (MFC) in unexplained recurrent miscarriages (URM). Mononuclear cells were isolated from the decidual tissues of URM cases and early pregnant women...
June 30, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28401935/unique-invariant-natural-killer-t-cells-promote-intestinal-polyps-by-suppressing-th1-immunity-and-promoting-regulatory-t-cells
#15
Y Wang, S Sedimbi, L Löfbom, A K Singh, S A Porcelli, S L Cardell
CD1d-restricted invariant natural killer T (iNKT) cells are known as potent early regulatory cells of immune responses. Besides the established roles in the regulation of inflammation and autoimmune disease, studies have shown that iNKT cells have important roles in tumor surveillance and the control of tumor metastasis. Here we found that the absence of iNKT cells markedly decreased the total number of intestinal polyps in APC(Min/+) mice, a model for colorectal cancer. Polyp iNKT cells were enriched for interleukin-10 (IL-10)- and IL-17-producing cells, showed a distinct phenotype being CD4(+), NK1...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28396308/new-options-and-controversies-in-the-management-of-chemotherapy-induced-nausea-and-vomiting
#16
Sara M Koth, Jill Kolesar
PURPOSE: An expanding array of options for prevention and treatment of chemotherapy-induced nausea and vomiting (CINV), including regimens containing olanzapine or recently approved neurokinin 1 (NK1) receptor antagonists, are reviewed. SUMMARY: Up to 80% of patients receiving chemotherapy have CINV. Current practice guidelines recommend that patients treated with highly emetogenic chemotherapy also receive a 3-drug antiemetic regimen initiated on the day of and continued for 3 days after chemotherapy administration, with the most commonly used 3-drug regimen consisting of an NK1 receptor antagonist, a 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, and dexamethasone...
June 1, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28388249/natural-killer-cell-subsets-and-their-functional-activity-in-beh%C3%A3-et-s-disease
#17
Fulya Cosan, Esin Aktas Cetin, Nilgun Akdeniz, Zeliha Emrence, Ayse Cefle, Gunnur Deniz
BACKGROUND: Behçet's disease (BD) is a rare, chronic autoinflammatory disorder of unknown origin. Natural killer (NK) cells are one of the major immunoregulatory cell groups of the innate immune system, but their role in BD pathogenesis is not well documented. OBJECTIVES: We aimed to investigate the role of NK cell subsets and their cytokine secretion and cytotoxic activity in patients with BD. PATIENTS AND METHODS: The study group consisted of BD patients who had only mucocutaneous involvement, and they were compared with healthy subjects...
April 7, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28386018/panin-neuroendocrine-cells-promote-tumorigenesis-via-neuronal-cross-talk
#18
Smrita Sinha, Ya-Yuan Fu, Adrien Grimont, Maren Ketcham, Kelly Lafaro, Joseph A Saglimbeni, Gokce Askan, Jennifer M Bailey, Jerry P Melchor, Yi Zhong, Min Geol Joo, Olivera Grbovic-Huezo, In-Hong Yang, Olca Basturk, Lindsey Baker, Young Park, Robert C Kurtz, David Tuveson, Steven D Leach, Pankaj J Pasricha
Nerves are a notable feature of the tumor microenvironment in some epithelial tumors, but their role in the malignant progression of pancreatic ductal adenocarcinoma (PDAC) is uncertain. Here, we identify dense innervation in the microenvironment of precancerous pancreatic lesions, known as pancreatic intraepithelial neoplasms (PanIN), and describe a unique subpopulation of neuroendocrine PanIN cells that express the neuropeptide substance P (SP) receptor neurokinin 1-R (NK1-R). Using organoid culture, we demonstrated that sensory neurons promoted the proliferation of PanIN organoids via SP-NK1-R signaling and STAT3 activation...
April 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28366470/ascending-projections-of-nociceptive-neurons-from-trigeminal-subnucleus-caudalis-a-population-approach
#19
Hiroto Saito, Ayano Katagiri, Shinji Okada, Lou Mikuzuki, Asako Kubo, Tatsuro Suzuki, Kinuyo Ohara, Jun Lee, Nobuhito Gionhaku, Toshimitsu Iinuma, David A Bereiter, Koichi Iwata
Second-order neurons in trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1) are critical for craniofacial pain processing and project rostrally to terminate in: ventral posteromedial thalamic nucleus (VPM), medial thalamic nuclei (MTN) and parabrachial nuclei (PBN). The contribution of each region to trigeminal nociception was assessed by the number of phosphorylated extracellular signal-regulated kinase-immunoreactive (pERK-IR) neurons co-labeled with fluorogold (FG). The phenotype of pERK-IR neurons was further defined by the expression of neurokinin 1 receptor (NK1)...
March 31, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28364631/synthetic-vaccine-nanoparticles-target-to-lymph-node-triggering-enhanced-innate-and-adaptive-antitumor-immunity
#20
Sun-Young Kim, Young-Woock Noh, Tae Heung Kang, Jung-Eun Kim, Sohyun Kim, Soong Ho Um, Doo-Byoung Oh, Yeong-Min Park, Yong Taik Lim
In this study, synthetic vaccine nanoparticles (SVNPs) that efficiently targeted lymph nodes, where immune responses against foreign antigens are primed, were developed to enhance antitumor immunity. The size (20-70 nm) and surface character (amination) of poly(γ-glutamic acid)-based SVNPs were selected for effective loading and delivery (i.e., migration and retention) of model tumor antigen (OVA) and toll-like receptor 3 agonist (poly (I:C)) to immune cells in lymph nodes. Antigen-presenting cells treated with SVNP-OVA and SVNP-IC showed higher uptake of OVA and poly (I:C) and higher secretion of inflammatory cytokines (TNF-α, IL-6) and type I interferon (IFN-α, IFN-β) than those treated with OVA and poly (I:C) alone...
June 2017: Biomaterials
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