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Cytokine signal transduction

Haruka Imai, Tsuyoshi Fujita, Mikihito Kajiya, Kazuhisa Ouhara, Tetsuya Yoshimoto, Shinji Matsuda, Katsuhiro Takeda, Hidemi Kurihara
BACKGROUND: An investigation of the mechanisms underlying the production of inflammatory cytokines through the stimulation of microorganisms on gingival epithelial cells may provide insights into the pathogenesis of the initiation of periodontitis. Lipid rafts, microdomains in the cell membrane, include a large number of receptors, and are centrally involved in signal transduction. We herein examined the involvement of lipid rafts in the expression of interleukin (IL-6) and IL-8 in gingival epithelial cells stimulated by periodontal pathogens...
October 17, 2016: Cellular Physiology and Biochemistry
Jennifer Jurkin, Corinna Krump, René Köffel, Christina Fieber, Christopher Schuster, Patrick M Brunner, Izabela Borek, Gregor Eisenwort, Clarice Lim, Jörg Mages, Roland Lang, Wolfgang Bauer, Diana Mechtcheriakova, Anastasia Meshcheryakova, Adelheid Elbe-Bürger, Georg Stingl, Herbert Strobl
BACKGROUND: Langerhans cell (LC) networks play key roles in immunity and tolerance at body surfaces. LCs are established prenatally and can be replenished from blood monocytes. Unlike skin-resident dermal/interstitial-type DCs (d/intDCs) and inflammatory dendritic epidermal cells (IDECs) appearing in dermatitis/eczema lesions, LCs lack key monocyte-affiliated markers. Inversely, LCs express various epithelial genes critical for their long-term peripheral tissue residency. OBJECTIVE: DCs are functionally involved in inflammatory diseases; however, mechanisms remained poorly understood...
October 11, 2016: Journal of Allergy and Clinical Immunology
Antonia Cianciulli, Rosaria Salvatore, Chiara Porro, Teresa Trotta, Maria Antonietta Panaro
We investigated the ability of folic acid to modulate the inflammatory responses of LPS activated BV-2 microglia cells and the signal transduction pathways involved. To this aim, the BV-2 cell line was exposed to LPS as a proinflammatory response inducer, in presence or absence of various concentrations of folic acid. The production of nitric oxide (NO) was determined by the Griess test. The levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-10 were determined by ELISA. Inducible NO synthase (iNOS), nuclear transcription factor-kappa B (NF-κB) p65, MAPKs protein, and suppressors of cytokine signaling (SOCS)1 and SOCS3 were analyzed by western blotting...
2016: Mediators of Inflammation
Yang-Yang He, Yu Yan, Hui-Fang Zhang, Yi-Huang Lin, Yu-Cai Chen, Yi Yan, Ping Wu, Jian-Song Fang, Shu-Hui Yang, Guan-Hua Du
Systemic lupus erythematosus (SLE), with a high incidence rate and insufficient therapy worldwide, is a complex disease involving multiple organs characterized primarily by inflammation due to deposition of immunocomplexes formed by production of autoantibodies. The mechanism of SLE remains unclear, and the disease still cannot be cured. We used pristane to induce SLE in female BALB/c mice. Methyl salicylate 2-O-β-d-lactoside (MSL; 200, 400, and 800 mg/kg) was orally administered 45 days after pristane injection for 4...
2016: Drug Design, Development and Therapy
Alicia R Mathers, Cara D Carey, Meaghan E Killeen, Julio Diaz-Perez, Sonia R Salvatore, Francisco J Schopfer, Bruce A Freeman, Louis D Falo
BACKGROUND: Reactions between nitric oxide (NO), nitrite (NO2(-) ), and unsaturated fatty acids give rise to electrophilic nitro-fatty acids (NO2 -FAs), such as nitro-oleic acid (OA-NO2 ) and nitro-linoleic acid (LNO2 ). Endogenous electrophilic fatty acids (EFAs) mediate anti-inflammatory responses by modulating metabolic and inflammatory signal transduction reactions. Hence, there is considerable interest in employing NO2 -FAs and other EFAs for the prevention and treatment of inflammatory disorders...
October 8, 2016: Allergy
André Schwambach Vieira, Dionéia Araldi, Elayne Vieira Dias, Filipe César do Prado, Claudia Herrera Tambeli, Carlos Amilcar Parada
Prostaglandin E2 (PGE2) is one of the major signaling molecules involved in hyperalgesia, acting directly on nociceptors and resulting in the activation of PKA and PKC. Once active, these kinases phosphorylate many cellular proteins, resulting in changes on nociceptors sensorial transduction properties. The Janus Kinases (JAKs) are a family of intracellular signaling molecules generally associated with cytokine signaling, and their activity can be increased in nociceptors after peripheral inflammation. However, there are no evidences of JAKs direct involvement in PGE2 mediated sensitization of nociceptors...
October 4, 2016: Life Sciences
Hong Lu
The liver is essential for survival due to its critical role in the regulation of metabolic homeostasis. Metabolism of xenobiotics, such as environmental chemicals and drugs by the liver protects us from toxic effects of these xenobiotics, whereas metabolism of cholesterol, bile acids (BAs), lipids, and glucose provide key building blocks and nutrients to promote the growth or maintain the survival of the organism. As a well-established master regulator of liver development and function, hepatocyte nuclear factor 4 alpha (HNF4α) plays a critical role in regulating a large number of key genes essential for the metabolism of xenobiotics, metabolic wastes, and nutrients...
September 2016: Acta Pharmaceutica Sinica. B
Chaohui Dai, Li Sun, Lihuai Yu, Guoqiang Zhu, Shenglong Wu, Wenbin Bao
As a critical adapter protein in Toll-like receptor (TLR)/Interleukin (IL)-1R signaling pathway, Myeloid differentiation protein 88 (MyD88) (plays an important role in immune responses and host defense against pathogens. This study was designed to provide a foundation and an important reagent for the mechanistic study of MyD88  and its role TLR/IL-1R signaling pathways in porcine immunity. Lentivirus-mediated RNAi was used to generate a porcine PK15 cell line with a silenced MyD88  gene and qPCR and Western blotting were used to detect changes in the expression of critical genes in the TLR4 signaling pathway...
October 5, 2016: Bioscience Reports
Jing Ye, Hao Zhang, Wen He, Bibo Zhu, Dengyuan Zhou, Zheng Chen, Usama Ashraf, Yanming Wei, Ziduo Liu, Zhen F Fu, Huanchun Chen, Shengbo Cao
Japanese encephalitis virus (JEV) is the leading cause of epidemic encephalitis worldwide. The pathogenesis of JEV is linked to a robust inflammatory response in the central nervous system (CNS). Glial cells are the resident immune cells in the CNS and represent critical effectors of CNS inflammation. To obtain a global overview of signaling events in glial cells during JEV infection, we conducted phosphoproteomics profiling of a JEV-infected glial cell line. We identified 1816 phosphopeptides, corresponding to 1264 proteins, that exhibited a change in phosphorylation status upon JEV infection...
October 4, 2016: Science Signaling
Pegah Abdollahi, Esten Nymoen Vandsemb, Magnus Aassved Hjort, Kristine Misund, Toril Holien, Anne-Marit Sponaas, Torstein B Ro, Tobias S Slordahl, Magne Borset
: Phosphatase of regenerating liver-3 (PTP4A3/PRL-3) is a dual specificity phosphatase that is up-regulated in various types of cancers and is related to poor prognosis and aggressive tumor behavior. The expression level of PRL-3 is elevated in response to several anti-apoptotic cytokines, including interleukin-6 (IL6), in cancer cells from patients with multiple myeloma (MM) and can promote survival and migration. Here it is demonstrated that PRL-3 activates Src kinase in the IL6-dependent MM cell line INA-6...
October 3, 2016: Molecular Cancer Research: MCR
Robert M Vogel, Amir Erez, Grégoire Altan-Bonnet
Despite progress in drug development, a quantitative and physiological understanding of how small-molecule inhibitors act on cells is lacking. Here, we measure the signalling and proliferative response of individual primary T-lymphocytes to a combination of antigen, cytokine and drug. We uncover two distinct modes of signalling inhibition: digital inhibition (the activated fraction of cells diminishes upon drug treatment, but active cells appear unperturbed), versus analogue inhibition (the activated fraction is unperturbed whereas activation response is diminished)...
2016: Nature Communications
Jin Li, Tamara Riedt, Steven Goossens, Carmen Carrillo García, Sabrina Szczepanski, Maria Brandes, Tim Pieters, Linne Dobrosch, Ines Gütgemann, Natalie Farla, Enrico Radaelli, Paco Hulpiau, Nikhil Mallela, Holger Fröhlich, Roberta La Starza, Caterina Matteucci, Tong Chen, Peter Brossart, Cristina Mecucci, Danny Huylebroeck, Jody J Haigh, Viktor Janzen
Epithelial-to-mesenchymal-transition (EMT) is critical for normal embryogenesis and effective post-natal wound healing, but is also associated with cancer metastasis. SNAIL, ZEB and TWIST families of transcription factors are key modulators of the EMT process, but their precise roles in adult hematopoietic development and homeostasis remain unclear. Here we report that genetic inactivation of Zeb2 results in increased frequency of stem and progenitor subpopulations within the bone marrow (BM) and spleen and that these changes accompany differentiation defects in multiple hematopoietic cell lineages...
September 28, 2016: Blood
Klaus Deckmann, Wolfgang Kummer
A peculiar cell type of the respiratory and gastrointestinal epithelia, originally termed "brush cell" or "tuft cell" by electron microscopists because of its apical tuft of microvilli, utilizes the canonical bitter taste transduction cascade known from oropharyngeal taste buds to detect potential hazardous compounds, e.g. bacterial products. Upon stimulation, this cell initiates protective reflexes and local inflammatory responses through release of acetylcholine and chemokines. Guided by the understanding of these cells as sentinels, they have been newly discovered at previously unrecognized anatomical locations, including the urethra...
September 29, 2016: Histochemistry and Cell Biology
Tao Tong, Ying Shen, Han-Woong Lee, Rina Yu, Taesun Park
Adenylyl cyclase 3 (Adcy3), a member of the mammalian adenylyl cyclase family responsible for generating the second messenger cAMP, has long been known to play an essential role in olfactory signal transduction. Here, we demonstrated that Adcy3 heterozygous null mice displayed increased visceral adiposity in the absence of hyperphagia and developed abnormal metabolic features characterized by impaired insulin sensitivity, dyslipidemia, and increased plasma levels of proinflammatory cytokines on both chow and high-fat diet (HFD)...
September 28, 2016: Scientific Reports
Wen-Qin Xu, Yu-Sheng Wang
Toll-like receptors (TLRs) are commonly referred to a series of evolutionary conserved receptors which recognize and respond to various microbes and endogenous ligands. Growing evidence has demonstrated that the expression of TLRs in the retina is regulated during retinal ischemic diseases, including ischemia-reperfusion injury, glaucoma, diabetic retinopathy (DR) and retinopathy of prematurity (ROP). TLRs can be expressed in multiple cells in the retina, such as glial cells, retinal pigment epithelium (RPE), as well as photoreceptor cells and endothelium cells...
2016: International Journal of Ophthalmology
Stefanie Dinner, Julian Kaltschmidt, Carolin Stump-Guthier, Svetlana Hetjens, Hiroshi Ishikawa, Tobias Tenenbaum, Horst Schroten, Christian Schwerk
Listeria monocytogenes, a Gram-positive bacterium, can cause meningitis after invading the human central nervous system. The blood-cerebrospinal fluid barrier (BCSFB), located at the epithelium of the choroid plexus, is a possible entry site for L. monocytogenes into the brain, and in vitro L. monocytogenes invades human choroid plexus epithelial papilloma (HIBCPP) cells. Although host cell signal transduction subsequent to infection by L. monocytogenes has been investigated, the role of mitogen-activated protein kinases (MAPK) is not clarified yet...
September 23, 2016: Microbes and Infection
Ying Chi, Junjie Cui, Youwei Wang, Wenjing Du, Fang Chen, Zongjin Li, Fengxia Ma, Baoquan Song, Fangyun Xu, Qingjun Zhao, Zhibo Han, Zhongchao Han
Numerous studies have demonstrated that interferon-γ (IFN-γ) is an important inflammatory cytokine, which may activate the immunomodulatory abilities of mesenchymal stem cells (MSCs), and may influence certain other functions of these cells. MicroRNAs are small non‑coding RNAs that regulate the majority of the biological functions of cells and are important in a variety of biological processes. However, few studies have been performed to investigate whether IFN‑γ affects the microRNA profile of MSCs...
September 19, 2016: Molecular Medicine Reports
Bénédicte Danis, Marijke van Rikxoort, Anita Kretschmann, Jiong Zhang, Patrice Godard, Lidija Andonovic, Franziska Siegel, Pitt Niehusmann, Etienne Hanon, Daniel Delev, Marec von Lehe, Rafal M Kaminski, Alexander Pfeifer, Patrik Foerch
Epilepsy is one of the most common neurological disorders characterized by recurrent seizures due to neuronal hyperexcitability. Here we compared miRNA expression patterns in mesial temporal lobe epilepsy with and without hippocampal sclerosis (mTLE + HS and mTLE -HS) to investigate the regulatory mechanisms differentiating both patient groups. Whole genome miRNA sequencing in surgically resected hippocampi did not reveal obvious differences in expression profiles between the two groups of patients. However, one microRNA (miR-184) was significantly dysregulated, which was confirmed by qPCR...
September 26, 2016: Scientific Reports
Qian Zhang, Ying Xiong, Guo-Bing Li, Qin Tang, Min Cao, Jing-Bin Huang, Mao Xing, Chang-Peng Hu, Ya Gong, Qing-Hua Wang, Ning Gao, Rong Zhang
ETHNOPHARMACOLOGICAL RELEVANCE: Xinqin, a polyherbal medicine, is an important traditional Chinese herbal formula used in traditional oriental medicine for treatment of allergic rhinitis (AR). The formula is based on the Chinese Pharmacopoeia. AIM OF THE STUDY: Previously, Xinqin exhibited potent anti-allergic effect in a guinea pig model of AR. In this study, we explored the molecular mechanism of the anti-allergic effect mediated by Xinqin. MATERIALS AND METHODS: AR was induced in guinea pigs (Hartley) with toluene-2, 4-diisocyanate (TDI) in vivo and in HMC-1 mast cells with A23187/ phorbol 12-myristate-13-acetate (PMA) in vitro...
September 22, 2016: Journal of Ethnopharmacology
Renate Burger, Andreas Guenther, Katja Klausz, Matthias Staudinger, Matthias Peipp, Eva Maria Murga Penas, Stefan Rose-John, John Wijdenes, Martin Gramatzki
Interleukin (IL)-6 has an important role in the pathophysiology of multiple myeloma where it supports the growth and survival of the malignant plasma cells in the bone marrow. It belongs to a family of cytokines which use the glycoprotein (gp)130 chain for signal transduction, such as oncostatin M or leukemia inhibitory factor (LIF). Targeting IL-6 in plasma cell diseases is currently evaluated in clinical trials with monoclonal antibodies (mAbs). Here, efforts were made to elucidate the contribution of IL-6 and gp130 signaling in malignant plasma cell growth in vivo...
September 22, 2016: Haematologica
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