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https://www.readbyqxmd.com/read/29235464/syk-kinase-mediates-brown-fat-differentiation-and-activation
#1
Marko Knoll, Sally Winther, Anirudh Natarajan, Huan Yang, Mengxi Jiang, Prathapan Thiru, Aliakbar Shahsafaei, Tony E Chavarria, Dudley W Lamming, Lei Sun, Jacob B Hansen, Harvey F Lodish
Brown adipose tissue (BAT) metabolism influences glucose homeostasis and metabolic health in mice and humans. Sympathetic stimulation of β-adrenergic receptors in response to cold induces proliferation, differentiation, and UCP1 expression in pre-adipocytes and mature brown adipocytes. Here we show that spleen tyrosine kinase (SYK) is upregulated during brown adipocyte differentiation and activated by β-adrenergic stimulation. Deletion or inhibition of SYK, a kinase known for its essential roles in the immune system, blocks brown and white pre-adipocyte proliferation and differentiation in vitro, and results in diminished expression of Ucp1 and other genes regulating brown adipocyte function in response to β-adrenergic stimulation...
December 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29232411/rev-erb-agonist-improves-adverse-cardiac-remodeling-and-survival-in-myocardial-infarction-through-an-anti-inflammatory-mechanism
#2
Endin Nokik Stujanna, Nobuyuki Murakoshi, Kazuko Tajiri, DongZhu Xu, Taizo Kimura, Rujie Qin, Duo Feng, Saori Yonebayashi, Yukino Ogura, Fumi Yamagami, Akira Sato, Akihiko Nogami, Kazutaka Aonuma
Rev-erb α, known as nuclear receptor 1D1 (NR1D1), regulates circadian rhythm, modulates glucose and lipid metabolism, and inflammatory response. However, little is known about the effect of Rev-erb agonist on the progression of myocardial infarction (MI) and heart failure. To investigate it, wild-type male mice underwent sham-operation or permanent ligation of the left anterior descending coronary artery to create MI model. Rev-erb agonist SR9009 (100 mg/kg/day) or vehicle was intraperitoneally administered...
2017: PloS One
https://www.readbyqxmd.com/read/29230225/sensing-lipids-with-mincle-structure-and-function
#3
REVIEW
Spencer J Williams
Mincle is a C-type lectin receptor that has emerged as an important player in innate immunity through its capacity to recognize a wide range of lipidic species derived from damaged/altered self and foreign microorganisms. Self-ligands include sterols (e.g., cholesterol), and β-glucosylceramides, and the protein SAP130, which is released upon cell death. Foreign lipids comprise those from both microbial pathogens and commensals and include glycerol, glucose and trehalose mycolates, and glycosyl diglycerides...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29228682/epidermal-ppar%C3%AE-influences-subcutaneous-tumor-growth-and-acts-through-tnf-%C3%AE-to-regulate-contact-hypersensitivity-and-the-acute-photoresponse
#4
Raymond L Konger, Ethel Derr-Yellin, Jeffrey B Travers, Jesus A Ocana, Ravi P Sahu
It is known that ultraviolet B (UVB) induces PPARγ ligand formation while loss of murine epidermal PPARγ (Pparg-/-epi) promotes UVB-induced apoptosis, inflammation, and carcinogenesis. PPARγ is known to suppress tumor necrosis factor-α (TNF-α) production. TNF-α is also known to promote UVB-induced inflammation, apoptosis, and immunosuppression. We show that Pparg-/-epi mice exhibit increased baseline TNF-α expression. Neutralizing Abs to TNF-α block the increased photo-inflammation and photo-toxicity that is observed in Pparg-/-epi mouse skin...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228322/tlr9-stimulation-induces-increase-in-fungicidal-activity-of-human-dendritic-cells-challenged-with-paracoccidioides-brasiliensis
#5
Ivy Rafacho Vieira, Reginaldo Keller Fernandes, Daniela Ramos Rodrigues, Carolina Mendonça Gorgulho, Ramon Kaneno, Ângela Maria Victoriano Campos Soares
Microorganisms killing by dendritic cells (DCs) is an important effector mechanism during innate immune response, as it can avoid dissemination of infection during migration of these cells toward draining lymph nodes. However, this function depends on pattern recognition receptors (PRRs) to which the microorganism will bind in these cells. Regarding this, TLR9 activation, by stimulating the oxidative metabolism, induces increase in microbicidal activity of these cells. Accordingly, we showed that DCs treatment with a TLR9 agonist results in an increase in fungicidal activity of these cells against the fungus Paracoccidioides brasiliensis (Pb), which however, was not associated to higher H2O2 levels...
December 8, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/29227167/diagnosis-of-platelet-function-disorders-a-standardized-rational-and-modular-flow-cytometric-approach
#6
Oliver Andres, Katja Henning, Gabriele Strauß, Annerose Pflug, Georgi Manukjan, Harald Schulze
A high proportion of patients with mucocutaneous bleeding diathesis and suspected inherited or acquired platelet disorder remain without diagnosis even after comprehensive laboratory testing. Since flow cytometry allows investigation of resting and activated platelets on the single cell level by requiring only minimal amounts of blood, this method has become an important assay within the diagnostic algorithm, especially in pediatrics. We therefore developed a standardized and modular flow cytometric approach that contributes to clarify impaired platelet function in a rational step-by-step manner...
December 11, 2017: Platelets
https://www.readbyqxmd.com/read/29226424/activation-of-ep2-receptor-suppresses-poly-i-c-and-lps-mediated-inflammation-in-primary-microglia-and-organotypic-hippocampal-slice-cultures-contributing-role-for-mapks
#7
Nizar M Yousif, Antonio Carlos Pinheiro de Oliveira, Simone Brioschi, Michael Huell, Knut Biber, Bernd L Fiebich
Brain inflammation is a critical factor involved in neurodegeneration. Recently, the prostaglandin E2 (PGE2 ) downstream members were suggested to modulate neuroinflammatory responses accompanying neurodegenerative diseases. In this study, we investigated the protective effects of prostaglandin E2 receptor 2 (EP2 ) during TLR3 and TLR4-driven inflammatory response using in vitro primary microglia and ex vivo organotypic hippocampal slice cultures (OHSCs). Depletion of microglia from OHSCs differentially affected TLR3 and TLR4 receptor expression...
December 11, 2017: Glia
https://www.readbyqxmd.com/read/29223154/antiinflammatory-effect-of-rosiglitazone-via-modulation-of-mrna-stability-of-interleukin-10-and-cyclooxygenase-2-in-astrocytes
#8
E V Pankevich, A A Astakhova, D V Chistyakov, M G Sergeeva
Investigation of molecular mechanisms of proinflammatory stimuli signaling in astrocytes is important for understanding their role in pathogenesis of central nervous system diseases as well as in functioning of the innate immunity system in non-immune cells. Here we show that lipopolysaccharide (LPS) stimulation of primary rat astrocytes led to conventional inflammatory response: increase in both proinflammatory (tumor necrosis factor, TNFα; prostaglandin E2, PGE2) and antiinflammatory marker (interleukin 10, IL-10) levels...
November 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/29222249/thrombocytopenia-in-pregnancy
#9
REVIEW
Douglas B Cines, Lisa D Levine
Thrombocytopenia develops in 5% to 10% of women during pregnancy or in the immediate postpartum period. A low platelet count is often an incidental feature, but it might also provide a biomarker of a coexisting systemic or gestational disorder and a potential reason for a maternal intervention or treatment that might pose harm to the fetus. This chapter reflects our approach to these issues with an emphasis on advances made over the past 5 to 10 years in understanding and managing the more common causes of thrombocytopenia in pregnancy...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29217133/pge2-suppresses-human-group-2-innate-lymphoid-cell-function
#10
Jovana Maric, Avinash Ravindran, Luca Mazzurana, Åsa K Björklund, Aline Van Acker, Anna Rao, Danielle Friberg, Sven-Erik Dahlén, Akos Heinemann, Viktoria Konya, Jenny Mjösberg
BACKGROUND: Group 2 innate lymphoid cells (ILC2) are involved in the initial phase of type 2 inflammation and can amplify allergic immune responses by orchestrating other type 2 immune cells. PGE2 is a bioactive lipid that plays protective roles in the lung, particularly during allergic inflammation. OBJECTIVE: We set out to investigate how PGE2 regulates human ILC2 function. METHODS: The effects of PGE2 on human ILC2 proliferation, intracellular cytokine and transcription factor expression were assessed by flow cytometry...
December 4, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29215956/effect-of-thrombopoietin-receptor-agonists-on-markers-of-coagulation-and-p-selectin-in-patients-with-immune-thrombocytopenia
#11
Lamya Garabet, Waleed Ghanima, Christine Monceyron Jonassen, Vibe Skov, René Holst, Marie-Christine Mowinckel, C Hasselbalc Hans, A Kruse Torben, Mads Thomassen, Howard Liebman, James B Bussel, Per Morten Sandset
Thrombopoietin-receptor-agonists (TPO-RA) are effective treatments of immune thrombocytopenia (ITP). Previous long-term TPO-RA clinical trials have shown that thrombotic events occurred in 6% of TPO-RA-treated ITP patients. To explore the increased risk of thrombosis, the effects of TPO-RA on markers of coagulation and P-selectin were studied. The study comprised two ITP cohorts and controls. Cohort 1 included 26 patients with sequential samples acquired before and during treatment with TPO-RA. Cohort 2 included a single sample in 18 patients on TPO-RA for more than one year...
December 7, 2017: Platelets
https://www.readbyqxmd.com/read/29213241/interaction-of-purinergic-p2x4-and-p2x7-receptor-subunits
#12
Markus Schneider, Kirsten Prudic, Anja Pippel, Manuela Klapperstück, Ursula Braam, Christa E Müller, Günther Schmalzing, Fritz Markwardt
P2X4 and P2X7 are members of the P2X receptor family, comprising seven isoforms (P2X1-P2X7) that form homo- and heterotrimeric non-specific cation channels gated by extracellular ATP. P2X4 and P2X7 are widely coexpressed, particularly in secretory epithelial cells and immune and inflammatory cells, and regulate inflammation and nociception. Although functional heteromerization has been established for P2X2 and P2X3 subunits expressed in sensory neurons, there are contradictory reports regarding a functional interaction between P2X4 and P2X7 subunits...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29212908/naive-cd4-t-cells-carrying-a-tlr2-agonist-overcome-tgf-%C3%AE-mediated-tumor-immune-evasion
#13
Mohsen Ibrahim, Davide Scozzi, Kelsey A Toth, Donatella Ponti, Daniel Kreisel, Cecilia Menna, Elena De Falco, Antonio D'Andrilli, Erino A Rendina, Antonella Calogero, Alexander S Krupnick, Andrew E Gelman
TLR agonists are effective at treating superficial cancerous lesions, but their use internally for other types of tumors remains challenging because of toxicity. In this article, we report that murine and human naive CD4+ T cells that sequester Pam3Cys4 (CD4+ TPam3) become primed for Th1 differentiation. CD4+ TPam3 cells encoding the OVA-specific TCR OT2, when transferred into mice bearing established TGF-β-OVA-expressing thymomas, produce high amounts of IFN-γ and sensitize tumors to PD-1/programmed cell death ligand 1 blockade-induced rejection...
December 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29211798/lipl21-lipoprotein-binding-to-peptidoglycan-enables-leptospira-interrogans-to-escape-nod1-and-nod2-recognition
#14
Gwenn Ratet, Ignacio Santecchia, Martine Fanton d'Andon, Frédérique Vernel-Pauillac, Richard Wheeler, Pascal Lenormand, Frédéric Fischer, Pierre Lechat, David A Haake, Mathieu Picardeau, Ivo G Boneca, Catherine Werts
Leptospirosis is a widespread zoonosis, potentially severe in humans, caused by spirochetal bacteria, Leptospira interrogans (L. interrogans). Host defense mechanisms involved in leptospirosis are poorly understood. Recognition of lipopolysaccharide (LPS) and lipoproteins by Toll-Like Receptors (TLR)4 and TLR2 is crucial for clearance of leptospires in mice, yet the role of Nucleotide Oligomerization Domain (NOD)-like receptors (NOD)1 and NOD2, recognizing peptidoglycan (PG) fragments has not previously been examined...
December 6, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29210987/prophylactic-sublingual-immunization-with-mycobacterium-tuberculosis-subunit-vaccine-incorporating-the-natural-killer-t-cell-agonist-alpha-galactosylceramide-enhances-protective-immunity-to-limit-pulmonary-and-extra-pulmonary-bacterial-burden-in-mice
#15
Arshad Khan, Shailbala Singh, Gloria Galvan, Chinnaswamy Jagannath, K Jagannadha Sastry
Infection by Mycobacterium tuberculosis (Mtb) remains a major global concern and the available Bacillus Calmette-Guerin (BCG) vaccine is poorly efficacious in adults. Therefore, alternative vaccines and delivery strategies focusing on Mtb antigens and appropriate immune stimulating adjuvants are needed to induce protective immunity targeted to the lungs, the primary sites of infections and pathology. We present here evidence in support of mucosal vaccination by the sublingual route in mice using the subunit Mtb antigens Ag85B and ESAT-6 adjuvanted with the glycolipid alpha-galactosylceramide (α-GalCer), a potent natural killer T (NKT) cell agonist...
December 6, 2017: Vaccines
https://www.readbyqxmd.com/read/29209310/alum-activates-the-bovine-nlrp3-inflammasome
#16
Ciaran Harte, Aoife L Gorman, S McCluskey, Michael Carty, Andrew G Bowie, C J Scott, Kieran G Meade, Ed C Lavelle
There has been a move away from vaccines composed of whole or inactivated antigens toward subunit-based vaccines, which although safe, provide less immunological protection. As a result, the use of adjuvants to enhance and direct adaptive immune responses has become the focus of much targeted bovine vaccine research. However, the mechanisms by which adjuvants work to enhance immunological protection in many cases remains unclear, although this knowledge is critical to the rational design of effective next generation vaccines...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29209309/new-directions-for-natural-killer-t-cells-in-the-immunotherapy-of-cancer
#17
Luc Teyton
Natural killer T (NKT) cells have been placed at the interface between innate and adaptive immunity by a long series of experiments that convincingly showed that beyond cytokine secretion and NK cell recruitment, NKT cells were coordinating dendritic cell and B cell maturation through direct membrane contacts and initiate productive responses. As such, NKT cells are the cellular adjuvant of many immune reactions and have functions that go much beyond what their name encapsulates. In addition, the initial discovery of the ligands of NKT cells is deeply linked to cancer biology and therapy...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29208743/latency-associated-expression-of-human-cytomegalovirus-us28-attenuates-cell-signaling-pathways-to-maintain-latent-infection
#18
Benjamin A Krishna, Emma L Poole, Sarah E Jackson, Martine J Smit, Mark R Wills, John H Sinclair
Reactivation of human cytomegalovirus (HCMV) latent infection from early myeloid lineage cells constitutes a threat to immunocompromised or immune-suppressed individuals. Consequently, understanding the control of latency and reactivation to allow targeting and killing of latently infected cells could have far-reaching clinical benefits. US28 is one of the few viral genes that is expressed during latency and encodes a cell surface G protein-coupled receptor (GPCR), which, during lytic infection, is a constitutive cell-signaling activator...
December 5, 2017: MBio
https://www.readbyqxmd.com/read/29207344/nod1-and-nod2-molecular-targets-in-prevention-and-treatment-of-infectious-diseases
#19
REVIEW
Mikhail V Pashenkov, Yulia A Dagil, Boris V Pinegin
Nucleotide-binding oligomerization domain (NOD) 1 and NOD2 are pattern-recognition receptors responsible for sensing fragments of bacterial peptidoglycan known as muropeptides. Stimulation of innate immunity by systemic or local administration of NOD1 and NOD2 agonists is an attractive means to prevent and treat infectious diseases. In this review, we discuss novel data concerning structural features of selective and non-selective (dual) NOD1 and NOD2 agonists, main signaling pathways and biological effects induced by NOD1 and NOD2 stimulation, including induction of pro-inflammatory cytokines, type I interferons and antimicrobial peptides, induction of autophagy, alterations of metabolism...
December 2, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29203707/extracellular-cell-stress-heat-shock-proteins-immune-responses-and-disease-an-overview
#20
REVIEW
A Graham Pockley, Brian Henderson
Extracellular cell stress proteins are highly conserved phylogenetically and have been shown to act as powerful signalling agonists and receptors for selected ligands in several different settings. They also act as immunostimulatory 'danger signals' for the innate and adaptive immune systems. Other studies have shown that cell stress proteins and the induction of immune reactivity to self-cell stress proteins can attenuate disease processes. Some proteins (e.g. Hsp60, Hsp70, gp96) exhibit both inflammatory and anti-inflammatory properties, depending on the context in which they encounter responding immune cells...
January 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
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