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How does proinflammatory cytokines

Eric Hatterer, Limin Shang, Pierre Simonet, Suzanne Herren, Bruno Daubeuf, Stéphanie Teixeira, James Reilly, Greg Elson, Robert Nelson, Cem Gabay, Jeremy Sokolove, Iain B McInnes, Marie Kosco-Vilbois, Walter Ferlin, Emmanuel Monnet, Cristina De Min
BACKGROUND: Increased expression of toll-like receptor 4 (TLR4) and its endogenous ligands, is characteristic of rheumatoid arthritis (RA) synovitis. In this study, we evaluated how these TLR4 ligands may drive pathogenic processes and whether the fine profiling of anti-citrullinated protein antibodies (ACPA) based on their target specificity might provide a simple means to predict therapeutic benefit when neutralizing TLR4 in this disease. METHODS: The capacity of RA synovial fluids (RASF) to stimulate cytokine production in monocytes from patients with RA was analyzed by ELISA...
October 6, 2016: Arthritis Research & Therapy
Lin-Wei Tsai, Yu-Chung Lin, Elena Perevedentseva, Andrei Lugovtsov, Alexander Priezzhev, Chia-Liang Cheng
Nanodiamonds (ND) have emerged to be a widely-discussed nanomaterial for their applications in biological studies and for medical diagnostics and treatment. The potentials have been successfully demonstrated in cellular and tissue models in vitro. For medical applications, further in vivo studies on various applications become important. One of the most challenging possibilities of ND biomedical application is controllable drug delivery and tracing. That usually assumes ND interaction with the blood system...
2016: International Journal of Molecular Sciences
Shrikant R Mulay, Santhosh V Kumar, Maciej Lech, Jyaysi Desai, Hans-Joachim Anders
The nephrons of the kidney are independent functional units harboring cells of a low turnover during homeostasis. As such, physiological renal cell death is a rather rare event and dead cells are flushed away rapidly with the urinary flow. Renal cell necrosis occurs in acute kidney injuries such as thrombotic microangiopathies, necrotizing glomerulonephritis, or tubular necrosis. All of these are associated with intense intrarenal inflammation, which contributes to further renal cell loss, an autoamplifying process referred to as necroinflammation...
May 2016: Seminars in Nephrology
K L Becker, V Aimanianda, X Wang, M S Gresnigt, A Ammerdorffer, C W Jacobs, R P Gazendam, L A B Joosten, M G Netea, J P Latgé, F L van de Veerdonk
UNLABELLED: Chitin is an important cell wall component of Aspergillus fumigatus conidia, of which hundreds are inhaled on a daily basis. Previous studies have shown that chitin has both anti- and proinflammatory properties; however the exact mechanisms determining the inflammatory signature of chitin are poorly understood, especially in human immune cells. Human peripheral blood mononuclear cells were isolated from healthy volunteers and stimulated with chitin from Aspergillus fumigatus Transcription and production of the proinflammatory cytokine interleukin-1β (IL-1β) and the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1Ra) were measured from the cell culture supernatant by quantitative PCR (qPCR) or enzyme-linked immunosorbent assay (ELISA), respectively...
2016: MBio
Richard Robinson
How does the body's immune system strike the delicate balance between under- and over-response? A new study shows that glucocorticoids limit the production of the proinflammatory cytokine interleukin-12 by dendritic cells in response to invading bacteria, thereby helping to avoid sepsis. Read the Research Article.
October 2015: PLoS Biology
Ghislaine Fontés, Julien Ghislain, Isma Benterki, Bader Zarrouki, Dominique Trudel, Yves Berthiaume, Vincent Poitout
Cystic fibrosis (CF) is the result of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). CF-related diabetes affects 50% of adult CF patients. How CFTR deficiency predisposes to diabetes is unknown. Herein, we examined the impact of the most frequent cftr mutation in humans, deletion of phenylalanine at position 508 (ΔF508), on glucose homeostasis in mice. We compared ΔF508 mutant mice with wild-type (WT) littermates. Twelve-week-old male ΔF508 mutants had lower body weight, improved oral glucose tolerance, and a trend toward higher insulin tolerance...
December 2015: Diabetes
I A Clark, B Vissel
This review concerns how the primary inflammation preceding the generation of certain key damage-associated molecular patterns (DAMPs) arises in Alzheimer's disease (AD). In doing so, it places soluble amyloid β (Aβ), a protein hitherto considered as a primary initiator of AD, in a novel perspective. We note here that increased soluble Aβ is one of the proinflammatory cytokine-induced DAMPs recognized by at least one of the toll-like receptors on and in various cell types. Moreover, Aβ is best regarded as belonging to a class of DAMPs, as do the S100 proteins and HMBG1, that further exacerbate production of these same proinflammatory cytokines, which are already enhanced, and induces them further...
August 2015: British Journal of Pharmacology
Julianne Stack, Sarah L Doyle, Dympna J Connolly, Line S Reinert, Kate M O'Keeffe, Rachel M McLoughlin, Søren R Paludan, Andrew G Bowie
Detection of microbes by TLRs on the plasma membrane leads to the induction of proinflammatory cytokines such as TNF-α, via activation of NF-κB. Alternatively, activation of endosomal TLRs leads to the induction of type I IFNs via IFN regulatory factors (IRFs). TLR4 signaling from the plasma membrane to NF-κB via the Toll/IL-1R (TIR) adaptor protein MyD88 requires the TIR sorting adaptor Mal, whereas endosomal TLR4 signaling to IRF3 via the TIR domain-containing adaptor-inducing IFN-β (TRIF) requires the TRIF-related adaptor molecule (TRAM)...
December 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
Jeanette C Valleau, Elinor L Sullivan
Leptin has long been associated with metabolism as it is a critical regulator of both food intake and energy expenditure, but recently, leptin dysregulation has been proposed as a mechanism of psychopathology. This review discusses the evidence supporting a role for leptin in mental health disorders and describes potential mechanisms that may underlie this association. Leptin plays a critical role in pregnancy and in fetal growth and development. Leptin's role and profile during development is examined in available human studies, and the validity of applying studies conducted in animal models to the human population are discussed...
November 2014: Journal of Chemical Neuroanatomy
Christian Beste, Janina Kneiphof, Dirk Woitalla
Neurosarcoidosis is a rare central nervous system manifestation of sarcoidosis. T cell, T-helper cell and macrophage activation via the major histocompatibility complex (MHC) II-mediated pathway causes this disease. Little is known about the possible cognitive disturbances in this disease as most reported instances are case studies. Here, we provide the first in-depth analysis of psychomotor functions in a sample of 30 neurosarcoidosis patients. We investigated action control processes using a paradigm that is able to examine how different tasks are cascaded to achieve the task goal...
October 2014: Brain, Behavior, and Immunity
Deirdre I De Ranieri, Linda Wagner-Weiner, Melissa Tesher, Hari Bandla, Karen Onel
BACKGROUND/PURPOSE: Children with JIA experience more pain and disordered sleep than healthy children. JIA and poor sleep are associated with particular cytokine abnormalities, and the correlation between the two and how they relate to a patient's pain perception have not been studied. Elevation in TNF-a, IL-6, IL-17, and IFN-g have been found in the serum of children with JIA during active disease. Levels of proinflammatory cytokines are also increased during sleep loss. Indeed, blocking TNF-a has been shown in adults with RA to improve sleep the night after the first dose...
March 2014: Arthritis & Rheumatology
Xiuju Dai, Hidenori Okazaki, Yasushi Hanakawa, Masamoto Murakami, Mikiko Tohyama, Yuji Shirakata, Koji Sayama
Eccrine sweat is secreted onto the skin's surface and is not harmful to normal skin, but can exacerbate eczematous lesions in atopic dermatitis. Although eccrine sweat contains a number of minerals, proteins, and proteolytic enzymes, how it causes skin inflammation is not clear. We hypothesized that it stimulates keratinocytes directly, as a danger signal. Eccrine sweat was collected from the arms of healthy volunteers after exercise, and levels of proinflammatory cytokines in the sweat were quantified by ELISA...
2013: PloS One
James W Neal, Philippe Gasque
The most devastating CNS bacterial infection, bacterial meningitis, has both acute and long-term neurologic consequences. The CNS defends itself against bacterial invasion through a combination of physical barriers (i.e. blood-brain barrier, meninges, and ependyma), which contain macrophages that express a range of pattern-recognition receptors that detect pathogens before they gain access to the CNS and cerebrospinal fluid. This activates an antipathogen response consisting of inflammatory cytokines, complement, and chemoattractants...
May 2013: Journal of Neuropathology and Experimental Neurology
Kenneth Michael Pollard, Dwight H Kono
There is substantial evidence that environmental triggers in combination with genetic and stochastic factors play an important role in spontaneous autoimmune disease. Although the specific environmental agents and how they promote autoimmunity remain largely unknown, in part because of diverse etiologies, environmentally induced autoimmune models can provide insights into potential mechanisms. Studies of idiopathic and environmentally induced systemic autoimmunity show that they are mediated by common adaptive immune response genes...
2013: BMC Medicine
C E Markhus, T V Karlsen, Marek Wagner, M Wagner, Ø S Svendsen, O Tenstad, K Alitalo, H Wiig
OBJECTIVE: The pathophysiology of lymphedema is incompletely understood. We asked how transcapillary fluid balance parameters and lymph flow are affected in a transgenic mouse model of primary lymphedema, which due to an inhibition of vascular endothelial growth factor receptor-3 (VEGFR-3) signaling lacks dermal lymphatics, and whether protein accumulation in the interstitium occurring in lymphedema results in inflammation. METHODS AND RESULTS: As estimated using a new optical-imaging technique, we found that this signaling defect resulted in lymph drainage in hind limb skin of K14-VEGFR-3-Ig mice that was 34% of the corresponding value in wild-type...
February 2013: Arteriosclerosis, Thrombosis, and Vascular Biology
Vecihi Batuman
Acute kidney injury in myeloma, a serious complication associated with poor prognosis, is generally mediated by the toxic and inflammatory effects of monoclonal free light chains (FLCs) on kidney proximal tubule cells and by the formation of intratubular casts through interaction with Tamm-Horsfall proteins. Production of excessive quantities of FLCs is seen in most cases of FLC-associated kidney injury, although a direct relation between quantity and nephrotoxicity does not exist, indicating variable toxicity among light chain species...
September 2012: Advances in Chronic Kidney Disease
Ana C Liberman, Maria Antunica-Noguerol, Viviane Ferraz-de-Paula, Joao Palermo-Neto, Carla N Castro, Jimena Druker, Florian Holsboer, Marcelo J Perone, Sarah Gerlo, Karolien De Bosscher, Guy Haegeman, Eduardo Arzt
BACKGROUND: Compound A (CpdA) is a dissociating non-steroidal glucocorticoid receptor (GR) ligand which has anti-inflammatory properties exerted by down-modulating proinflammatory gene expression. By favouring GR monomer formation, CpdA does not enhance glucocorticoid (GC) response element-driven gene expression, resulting in a reduced side effect profile as compared to GCs. Considering the importance of Th1/Th2 balance in the final outcome of immune and inflammatory responses, we analyzed how selective GR modulation differentially regulates the activity of T-bet and GATA-3, master drivers of Th1 and Th2 differentiation, respectively...
2012: PloS One
Jan Piet van Hamburg, Patrick S Asmawidjaja, Nadine Davelaar, Adriana M C Mus, Ferry Cornelissen, Johannes P T M van Leeuwen, Johanna M W Hazes, Radboud J E M Dolhain, Pieter A G M Bakx, Edgar M Colin, Erik Lubberts
OBJECTIVES: T helper 17 (Th17) cells from patients with early rheumatoid arthritis (RA) induce a proinflammatory feedback loop upon RA synovial fibroblast (RASF) interaction, including autocrine interleukin (IL)-17A production. A major challenge in medicine is how to control the pathogenic Th17 cell activity in human inflammatory autoimmune diseases. The objective of this study was to examine whether tumour necrosis factor (TNF) blockade and/or 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) controls Th17-mediated synovial inflammation...
April 2012: Annals of the Rheumatic Diseases
Jesper A B Strickertsson, Kristina B V Døssing, Anna J M Aabakke, Hans-Olof Nilsson, Thomas V O Hansen, Ulrich Knigge, Andreas Kjær, Torkel Wadström, Lennart Friis-Hansen
AIM: To investigate if and how the proinflammatory cytokine interferon γ (IFNγ) affects ghrelin expression in mice. METHODS: The plasma concentration of ghrelin, and gastric ghrelin and somatostatin expression, were examined in wild-type mice and mice infected with Helicobacter pylori (H. pylori). Furthermore, ghrelin expression was examined in two achlorhydric mouse models with varying degrees of gastritis due to bacterial overgrowth. To study the effect of IFNγ alone, mice were given a subcutaneous infusion of IFNγ for 7 d...
July 14, 2011: World Journal of Gastroenterology: WJG
Heather J Galipeau, Nestor E Rulli, Jennifer Jury, Xianxi Huang, Romina Araya, Joseph A Murray, Chella S David, Fernando G Chirdo, Kathy D McCoy, Elena F Verdu
Celiac disease (CD) is frequently diagnosed in patients with type 1 diabetes (T1D), and T1D patients can exhibit Abs against tissue transglutaminase, the auto-antigen in CD. Thus, gliadin, the trigger in CD, has been suggested to have a role in T1D pathogenesis. The objective of this study was to investigate whether gliadin contributes to enteropathy and insulitis in NOD-DQ8 mice, an animal model that does not spontaneously develop T1D. Gliadin-sensitized NOD-DQ8 mice developed moderate enteropathy, intraepithelial lymphocytosis, and barrier dysfunction, but not insulitis...
October 15, 2011: Journal of Immunology: Official Journal of the American Association of Immunologists
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