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Xingxing Yu, Lingling Xu, Yingjun Chang, Xiaojun Huang, Xiangyu Zhao
The balance between immunostimulation and immunoregulation in T cell immunity is achieved by maintaining specific ratios of Th1, Th2, Th3 and Tr1 cells. Here, we investigate levels of type 1 (IFN-gamma; NK1), type 2 (IL-13; NK2), type 3 (TGF-beta; NK3) and regulatory (IL-10; NKr) cytokines in peripheral blood to assess the cytokine profiles of natural killer (NK) cells following human allogeneic hematopoietic stem cell transplantation (allo-HSCT). NK2 and NK3 cell expansion was observed after allo-HSCT; levels of NKr cells reached donor levels at day 15, though levels of NK1 cells were consistently lower than donor levels until day 60 after allo-HSCT...
March 9, 2018: Science China. Life Sciences
Brittany P Lassiter, Siqi Guo, Stephen J Beebe
Nano-pulse stimulation (NPS), previously called nsPEFs, induced a vaccine-like effect after ablation of orthotopic N1-S1 hepatocellular carcinoma (HCC), protecting rats from subsequent challenges with N1-S1 cells. To determine immunity, immune cell phenotypes were analyzed in naïve, treated and protected rats. NPS provides a positive, post-ablation immuno-therapeutic outcome by alleviating immunosuppressive T regulatory cells (Treg) in the tumor microenvironment (TME), allowing dendritic cell influx and inducing dynamic changes in natural killer cells (NKs), NKT-cells and T-lymphocytes in blood, spleen and liver...
March 13, 2018: Cancers
Kenneth D Clevenger, Rosa Ye, Jin Woo Bok, Paul M Thomas, Md Nurul Islam, Galen P Miley, Matthew Robey, Cynthia Chen, KaHoua Yang, Michael Swyers, Edward Wu, Peng Gao, Chengcang Wu, Nancy P Keller, Neil L Kelleher
The benzodiazepine benzomalvin A/D is a fungal-derived specialized metabolite and inhibitor of the substance P receptor NK1, biosynthesized by a three-gene non-ribosomal peptide synthetase cluster. Here, we utilize <u>f</u>ungal <u>a</u>rtificial <u>c</u>hromosomes with <u>m</u>etabolomic <u>s</u>coring (FAC-MS) to carry out molecular genetic pathway dissection and targeted metabolomics analysis to assign the in vivo role of each domain in the benzomalvin biosynthetic pathway...
March 13, 2018: Biochemistry
Yasuyuki Negishi, Tomoko Ichikawa, Toshiyuki Takeshita, Hidemi Takahashi
Unexpected fetal loss is one of the common complications of pregnancy; however, the pathogenesis of many miscarriages, particularly those not associated with infections, is unknown. We previously found that activated DEC-205+ dendritic cells (DCs) and NK1.1+ invariant natural killer T (iNKT) cells are recruited into the myometrium of mice when miscarriage is induced by the intraperitoneal administration of α-galactosylceramide (α-GalCer). Here we demonstrate that the adoptive transfer of DEC-205+ bone marrow-derived DCs cocultured with α-GalCer (DEC-205+ BMDCs-c/w-α-GalCer) directly induced marked fetal loss by syngeneic pregnant C57BL/6 (B6) mice and allogeneic mice (B6 (♀) × BALB/c (♂)), which was accompanied by the accumulation of activated iNKT cells in the myometrium...
March 9, 2018: European Journal of Immunology
M C Carvalho, A C Veloni, K Genaro, M L Brandão
A single threatening experience may change the behavior of an animal in a long-lasting way and elicit generalized behavioral responses to a novel threatening situation that is unrelated to the original aversive experience. Electrical stimulation (ES) of the dorsal periaqueductal gray (dPAG) produces a range of defensive reactions, characterized by freezing, escape, and post-stimulation freezing (PSF). The latter reflects the processing of ascending aversive information to prosencephalic structures, including the central nucleus of the amygdala (CeA), which allows the animal to evaluate the consequences of the aversive situation...
February 2018: Neurobiology of Learning and Memory
Andrew Kimball, Matthew Schaller, Amrita Joshi, Frank Davis, Aaron denDekker, Anna Boniakowski, Jennifer Bermick, Andrea Obi, Bethany Moore, Peter K Henke, Steve L Kunkel, Katherine A Gallagher
OBJECTIVE: Wound monocyte-derived macrophage plasticity controls the initiation and resolution of inflammation that is critical for proper healing, however, in diabetes mellitus, the resolution of inflammation fails to occur. In diabetic wounds, the kinetics of blood monocyte recruitment and the mechanisms that control in vivo monocyte/macrophage differentiation remain unknown. APPROACH AND RESULTS: Here, we characterized the kinetics and function of Ly6CHi [Lin- (CD3- CD19- NK1...
March 1, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Marie Indrová, Joanna Rossowska, Elzbieta Pajtasz-Piasecka, Romana Mikyšková, Jan Richter, Jozef Rosina, Radislav Sedlacek, Anna Fišerová
The present study aimed to elucidate the role of cluster of differentiation (CD)8+, CD4+, natural killer (NK), and myeloid (CD11b+) cells in the course of the growth and rejection of experimental major histocompatibility complex (MHC) class I-deficient, HPV16 E6/E7-associated TC-1/A9 tumors in mice. Stable mouse lines (F30 ) generated by inbreeding of Balb/c and C57BL/6 strains, which were characterized by H-2Db+d-NK1.1neg (B6-neg) and H-2Db-d+NK1.1high (Balb-high) phenotypes, were used for the present study...
March 2018: Oncology Letters
Duy-Khanh Dang, Eun-Joo Shin, Dae-Joong Kim, Hai-Quyen Tran, Ji Hoon Jeong, Choon-Gon Jang, Seung-Yeol Nah, Jung Hwan Jeong, Jae Kyung Byun, Sung Kwon Ko, Guoying Bing, Jau-Shyong Hong, Hyoung-Chun Kim
BACKGROUND: We previously reported that ginsenoside Re (GRe) attenuated against methamphetamine (MA)-induced neurotoxicity via anti-inflammatory and antioxidant potentials. We also demonstrated that dynorphin possesses anti-inflammatory and antioxidant potentials against dopaminergic loss, and that balance between dynorphin and substance P is important for dopaminergic neuroprotection. Thus, we examined whether GRe positively affects interactive modulation between dynorphin and substance P against MA neurotoxicity in mice...
February 21, 2018: Journal of Neuroinflammation
Margriet Roelse, Maurice G L Henquet, Harrie A Verhoeven, Norbert C A de Ruijter, Ron Wehrens, Marco S van Lenthe, Renger F Witkamp, Robert D Hall, Maarten A Jongsma
Reverse-transfected cell arrays in microfluidic systems have great potential to perform large-scale parallel screening of G protein-coupled receptor (GPCR) activation. Here, we report the preparation of a novel platform using reverse transfection of HEK293 cells, imaging by stereo-fluorescence microscopy in a flowcell format, real-time monitoring of cytosolic calcium ion fluctuations using the fluorescent protein Cameleon and analysis of GPCR responses to sequential sample exposures. To determine the relationship between DNA concentration and gene expression, we analyzed cell arrays made with variable concentrations of plasmid DNA encoding fluorescent proteins and the Neurokinin 1 (NK1) receptor...
February 16, 2018: Sensors
Gil Yosipovitch, Sonja Ständer, Matthew B Kerby, James W Larrick, Andrew J Perlman, Edward F Schnipper, Xiaoming Zhang, Jean Y Tang, Thomas Luger, Martin Steinhoff
BACKGROUND: The substance P/neurokinin 1 receptor (NK1 R) pathway is critical in chronic pruritus; anecdotal evidence suggests antagonism of this pathway can reduce chronic itch. OBJECTIVE: To assess the safety and efficacy of the NK1 R antagonist serlopitant in treating chronic pruritus. METHODS: Eligible patients with severe chronic pruritus who were refractory to antihistamines or topical steroids were randomized to serlopitant 0.25, 1, or 5 mg, or placebo, administered once daily for 6 weeks as monotherapy or with midpotency steroids and emollients...
February 17, 2018: Journal of the American Academy of Dermatology
Eszter Pakai, Valeria Tekus, Csaba Zsiboras, Zoltan Rumbus, Emoke Olah, Patrik Keringer, Nora Khidhir, Robert Matics, Laszlo Deres, Katalin Ordog, Nikolett Szentes, Krisztina Pohoczky, Agnes Kemeny, Peter Hegyi, Erika Pinter, Andras Garami
Neurokinin (NK) signaling is involved in various inflammatory processes. A common manifestation of systemic inflammation is fever, which is usually induced in animal models with the administration of bacterial lipopolysaccharide (LPS). A role for the NK1 receptor was shown in LPS-induced fever, but the underlying mechanisms of how the NK1 receptor contributes to febrile response, especially in the early phase, have remained unknown. We administered LPS (120 µg/kg, intraperitoneally) to mice with the Tacr1 gene, i...
2018: Frontiers in Immunology
Eline Haspeslagh, Mary J van Helden, Kim Deswarte, Sofie De Prijck, Justine van Moorleghem, Louis Boon, Hamida Hammad, Eric Vivier, Bart N Lambrecht
House dust mite (HDM)-allergic asthma is driven by T helper 2 (Th2) lymphocytes, but also innate immune cells control key aspects of the disease. The precise function of innate natural killer (NK) cells during the initiation and propagation of asthma has been very confusing, in part because different, not entirely specific, strategies were used to target these cells. We show that HDM inhalation rapidly led to the accumulation of NK cells in the lung-draining lymph nodes and of activated CD69 + NK cells in the bronchoalveolar lumen...
February 14, 2018: EMBO Molecular Medicine
Huali Wu, Yucheng Zhao, Qiaoling Huang, Minxuan Cai, Qi Pan, Mengsi Fu, Xiaohong An, Zhenjiang Xia, Meng Liu, Yu Jin, Ling He, Jing Shang
Substance P (SP) is a candidate mediator along the brain-skin axis and can mimic the effects of stress to regulate melanogenesis. Previously, we and others have found that the regulation of SP for pigmentary function was mediated by neurokinin 1 receptor (NK1R). Emerging evidence has accumulated that psychologic stress can induce dysfunction in the cutaneous serotonin 5-hydroxytryptamine (5-HT)-5-HT1A/1B receptor system, thereby resulting in skin hypopigmentation. Moreover, NK1R and 5-HTR (except 5-HT3) belong to GPCR...
February 7, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Kouichi Yamamoto, Atsushi Yamatodani
INTRODUCTION: Pica behavior, kaolin ingestion, in rats and mice can be used as an assessment of nausea and vomiting; however, we observed that the incidence of pica behavior in ICR strain mice varied markedly. We investigated the susceptibility of four strains of mice (ICR, BALB/c, C57BL/6, and DBA/2) to the development of pica behavior. METHODS: Mice received cisplatin (7.5 mg/kg, i.p.) with or without a serotonin 5-HT3 receptor antagonist (granisetron: 0.1 mg/kg, i...
January 30, 2018: Journal of Pharmacological and Toxicological Methods
Maho Tsubota, Yasumasa Okawa, Yuhei Irie, Mariko Maeda, Tomoka Ozaki, Fumiko Sekiguchi, Hiroyasu Ishikura, Atsufumi Kawabata
Hydrogen sulfide (H2 S) formed by cystathionine-γ-lyase (CSE) enhances the activity of Cav 3.2 T-type Ca2+ channels, contributing to the bladder pain accompanying hemorrhagic cystitis caused by systemic administration of cyclophosphamide (CPA) in mice. Given clinical and fundamental evidence for the involvement of the substance P/NK1 receptor systems in bladder pain syndrome (BPS)/interstitial cystitis (IC), we created an intravesical substance P-induced bladder pain model in mice and analyzed the possible involvement of the CSE/Cav 3...
January 31, 2018: Neuropharmacology
Fiona M Bright, Roger W Byard, Robert Vink, David S Paterson
Substance P (SP) and its tachykinin NK1 receptor (NK1R) function within key medullary nuclei to regulate cardiorespiratory and autonomic control. We examined the normative distribution of SP and NK1R in the serotonergic (5-Hydroxytryptamine, [5-HT]) network of the human infant medulla during postnatal development, to provide a baseline to facilitate future analysis of the SP/NK1R system and its interaction with 5-HT within pediatric brainstem disorders in early life. [125I] labelled Bolton Hunter SP (BH-SP) tissue receptor autoradiography (n = 15), single label immunohistochemistry (IHC) and double label immunofluorescence (IF) (n = 10) were used to characterize the normative distribution profile of SP and NK1R in the 5-HT network of the human infant medulla during postnatal development...
January 10, 2018: Brain Research Bulletin
Anthony Y Huang, Sandy Y Wu
BACKGROUND AND PURPOSE: Capsaicin-mediated modulation on taste nerve responses is thought to be produced indirectly by actions of neuropeptides, e.g., calcitonin gene-related peptide (CGRP) and substance P (SP), onto taste cells implying playing a role in taste sensitivity. During processing gustatory information in taste buds, CGRP shapes peripheral taste signals via serotonergic signaling. The underlying assumption has been that SP exerts its effects on taste transmitter secretion in taste buds of mice...
January 12, 2018: British Journal of Pharmacology
I R Dunay, A Diefenbach
Innate lymphoid cells (ILCs) are a group of lymphocytes that carry out important functions in immunity to infections and in organ homeostasis at epithelial barrier surfaces. ILCs are innate immune cells that provide an early source of cytokines to initiate immune responses against pathogens. Cytotoxic ILCs (i.e. conventional (c)NK cells) and several subsets of helper-like ILCs are the major branches of the ILC family. Conventional NK cells and group 1 ILCs share several characteristics such as surface receptors and the ability to produce IFN-γ upon activation, but they differ in their developmental paths and in their dependence on specific transcription factors...
February 2018: Parasite Immunology
Nicole G Barra, Isabella Y Fan, Jenna B Gillen, Marianne Chew, Katarina Marcinko, Gregory R Steinberg, Martin J Gibala, Ali A Ashkar
High intensity interval training (HIIT) boosts natural killer (NK) cell number and activity in normal weight breast cancer patients; however, whether this occurs in obese individuals is not well established. The goal of this study was to determine whether HIIT effectively boosts NK cells as a therapeutic strategy against breast cancer in an obese mouse model and in overweight/obese women. Diet induced female C57Bl/6 obese mice were assigned to undergo HIIT for four weeks or remain sedentary. Female participants were subjected to a six weeks HIIT protocol...
December 2017: Journal of Cancer Prevention
Nadia M J Rupniak, Mary Katofiasc, Lesley Marson, Karl B Thor
Tachykinin NK2 receptor (NK2R) agonists have potential to alleviate clinical conditions associated with bladder and gastrointestinal under activity. The effects of agonists with differing selectivity for NK2R over NK1Rs on colorectal, bladder, and cardiovascular function were examined in anesthetized dogs. Intravenous (IV) administration of NKA, LMN-NKA ([Lys5,MeLeu9,Nle10]-NKA(4-10)), and [β-Ala8]-NKA(4-10) caused a dose-related increase in colorectal pressure (up to 98 mmHg) that was blocked by pretreatment with the NK2R antagonist GR 159897 (1 mg/kg), and hypotension (decrease in mean arterial pressure of ~40 mmHg) that was blocked by the NK1R antagonist CP-99,994 (1 mg/kg)...
December 26, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
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