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Type 2 inflammation

Julia J Mack, M Luisa Iruela-Arispe
PURPOSE OF REVIEW: The formation of a hierarchical vascular network is a complex process that requires precise temporal and spatial integration of several signaling pathways. Amongst those, Notch has emerged as a key regulator of multiple steps that expand from endothelial sprouting to arterial specification and remains relevant in the adult. This review aims to summarize major concepts and rising hypotheses on the role of Notch signaling in the endothelium. RECENT FINDINGS: A wealth of new information has helped to clarify how Notch signaling cooperates with other pathways to orchestrate vascular morphogenesis, branching, and function...
March 14, 2018: Current Opinion in Hematology
Victoria Sundblad, Amado A Quintar, Luciano G Morosi, Sonia I Niveloni, Ana Cabanne, Edgardo Smecuol, Eduardo Mauriño, Karina V Mariño, Julio C Bai, Cristina A Maldonado, Gabriel A Rabinovich
Galectins, a family of animal lectins characterized by their affinity for N-acetyllactosamine-enriched glycoconjugates, modulate several immune cell processes shaping the course of innate and adaptive immune responses. Through interaction with a wide range of glycosylated receptors bearing complex branched N-glycans and core 2-O-glycans, these endogenous lectins trigger distinct signaling programs thereby controling immune cell activation, differentiation, recruitment and survival. Given the unique features of mucosal inflammation and the differential expression of galectins throughout the gastrointestinal tract, we discuss here key findings on the role of galectins in intestinal inflammation, particularly Crohn's disease, ulcerative colitis, and celiac disease (CeD) patients, as well as in murine models resembling these inflammatory conditions...
2018: Frontiers in Immunology
Brendan M Everett, Marc Y Donath, Aruna D Pradhan, Tom Thuren, Prem Pais, Jose C Nicolau, Robert J Glynn, Peter Libby, Paul M Ridker
BACKGROUND: Subclinical inflammation mediated in part by interleukin-1 beta (IL-1β) participates in peripheral insulin resistance and impaired pancreatic insulin secretion. OBJECTIVES: We tested the hypothesis that canakinumab, an IL-1β inhibitor, reduces incident diabetes. METHODS: The Canakinumab Antiinflammatory Thrombosis Outcomes Study (CANTOS) randomized 10,061 patients with prior MI and high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L to placebo or canakinumab at doses of 50mg, 150mg, or 300mg subcutaneously once every three months...
March 3, 2018: Journal of the American College of Cardiology
Tomáš Vaisar, Erica Couzens, Arnold Hwang, Michael Russell, Carolyn E Barlow, Laura F DeFina, Andrew N Hoofnagle, Francis Kim
AIMS/HYPOTHESIS: One of the hallmarks of diabetes is impaired endothelial function. Previous studies showed that HDL can exert protective effects on endothelium stimulating NO production and protecting from inflammation and suggested that HDL in obese people with diabetes and dyslipidemia may have lower endothelial protective function. We aimed to investigate whether type 2 diabetes impairs HDL endothelium protective functions in people with otherwise normal lipid profile. METHODS: In a case-control study (n = 41 per group) nested in the Cooper Center Longitudinal Study we tested the ability of HDL to protect endothelium by stimulating endothelial nitric oxide synthase activity and suppressing NFκB-mediated inflammatory response in endothelial cells...
2018: PloS One
Xiumei Che, Ki Cheong Park, Soo Jung Park, You Hyun Kang, Hyun A Jin, Joo Wan Kim, Dong Hyuk Seo, Dae Kyu Kim, Tae Il Kim, Won Ho Kim, Seung Won Kim, Jae Hee Cheon
Triggering receptor expressed on myeloid cells 1 (TREM-1)-expressing intestinal macrophages are significantly increased in the colons of patients with inflammatory bowel disease (IBD). We focused here on the effects of guggulsterone on macrophage modulation in colitis as a potential therapeutic molecule in human IBD and explore the underlying mechanisms. Gene expression in macrophages was examined and wound healing assay using HT-29 cells was performed. Colitis in wild type and IL-10-, TLR4-, and MyD88-deficient mice was induced via the administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) into the colon...
March 15, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Lisa K Gouwens, Mudar S Ismail, Victoria A Rogers, Nathan T Zeller, Evan C Garrad, Fatima S Amtashar, Nyasha J Makoni, David C Osborn, Michael R Nichols
Microvesicles (MVs) and exosomes comprise a class of cell-secreted particles termed extracellular vesicles (EVs). These cargo-holding vesicles mediate cell-to-cell communication and have recently been implicated in neurodegenerative diseases such as Alzheimer's disease (AD). The two types of EVs are distinguished by the mechanism of cell release and their size, with the smaller exosomes and the larger MVs ranging from 30 to 100 nm and 100 nm to 1 μm in diameter, respectively. MV numbers are increased in AD and appear to interact with amyloid-β peptide (Aβ), the primary protein component of the neuritic plaques in the AD brain...
March 15, 2018: ACS Chemical Neuroscience
Keiichi Koizumi, Minako Hoshiai, Nobuyuki Katsumata, Takako Toda, Hiroaki Kise, Yohei Hasebe, Yosuke Kono, Yuto Sunaga, Masashi Yoshizawa, Atsushi Watanabe, Keiko Kagami, Masako Abe, Kanji Sugita
BACKGROUND: The effect of infliximab (IFX) on immune cells has not been fully reported in Kawasaki disease (KD). To investigate the mechanism of IFX in KD, we examined changes in the abundance of CD14+ CD16+ activated monocytes, regulatory T cells (Treg ), and T-helper cell type 17 (Th17) cells following treatment with IFX. METHODS: We collected peripheral blood from patients with intravenous immunoglobulin (IVIG)-resistant KD and analyzed the absolute counts of CD14+ CD16+ monocytes, Treg cells (CD4+ CD25+ FOXP3+ ) and Th17 cells (CD4+ IL-17A+ ) by flow cytometry...
March 15, 2018: Pediatrics International: Official Journal of the Japan Pediatric Society
Paola Cipriani, Vasiliky Liakouli, Francesco Carubbi, Onorina Berardicurti, Paola Di Benedetto, Francesco Ciccia, Giuliana Guggino, Saverio Alvaro, Giovanni Triolo, Roberto Giacomellia, Piero Ruscitti
BACKGROUND: Although in the past, prevention of the joint destruction and disability were strongly emphasised in rheumatoid arthritis (RA), at present, a growing body of evidence is focused at identifying the best management of associated comorbidities, such as type 2 diabetes (T2D). Recently, the hypothesis that blocking pro-inflammatory activity may be helpful in the treatment of some comorbidities has been proposed in RA patients. OBJECTIVE: We reviewed the role of IL-1β during RA and T2D, the efficacy of IL-1 blocking agents in controlling both diseases and, possible, decreasing the concomitant enhanced atherosclerotic process...
March 13, 2018: Reviews on Recent Clinical Trials
Chia-Yen Dai, Yi-Shan Tsai, Wen-Wen Chou, Tawei Liu, Chung-Feng Huang, Shu-Chi Wang, Pei-Chien Tsai, Ming-Lun Yeh, Ming-Yen Hsieh, Ching-I Huang, Shang-Yin Vanson Liu, Jee-Fu Huang, Wan-Long Chuang, Ming-Lung Yu
Background/Aims: MicroRNA-125b (miR-125b) has been found to regulate inflammation and acts as an oncogene in many cancers. The mechanisms of miR-125b expression during hepatitis C virus (HCV) infection remain to be clarified. The present study aims to identify the factors that might regulate miR-125b expression in HCV infection. Results: High expression of miR-125b was found to correlate with HCV infection in replicon cells and in sera from HCV-infected patients, whereas the miR-125b inhibitor reduced HCV gene expression...
February 16, 2018: Oncotarget
Dimity H Ball, Lamyaa Al-Riyami, William Harnett, Margaret M Harnett
ES-62 is a secreted parasitic worm-derived immunomodulator that exhibits therapeutic potential in allergy by downregulating aberrant MyD88 signalling to normalise the inflammatory phenotype and mast cell responses. IL-33 plays an important role in driving mast cell responses and promoting type-2 allergic inflammation, particularly with respect to asthma, via MyD88-integrated crosstalk amongst the IL-33 receptor (ST2), TLR4 and FcεRI. We have now investigated whether ES-62 targets this pathogenic network by subverting ST2-signalling, specifically by characterising how the functional outcomes of crosstalk amongst ST2, TLR4 and FcεRI are modulated by the worm product in wild type and ST2-deficient mast cells...
March 14, 2018: Scientific Reports
Stefan Roth, Vikramjeet Singh, Steffen Tiedt, Lisa Schindler, Georg Huber, Arie Geerlof, Daniel J Antoine, Antoine Anfray, Cyrille Orset, Maxime Gauberti, Antoine Fournier, Lesca M Holdt, Helena Erlandsson Harris, Britta Engelhardt, Marco E Bianchi, Denis Vivien, Christof Haffner, Jürgen Bernhagen, Martin Dichgans, Arthur Liesz
Stroke induces a multiphasic systemic immune response, but the consequences of this response on atherosclerosis-a major source of recurrent vascular events-have not been thoroughly investigated. We show that stroke exacerbates atheroprogression via alarmin-mediated propagation of vascular inflammation. The prototypic brain-released alarmin high-mobility group box 1 protein induced monocyte and endothelial activation via the receptor for advanced glycation end products (RAGE)-signaling cascade and increased plaque load and vulnerability...
March 14, 2018: Science Translational Medicine
Davide Di Fusco, Vincenzo Dinallo, Ivan Monteleone, Federica Laudisi, Irene Marafini, Eleonora Franzè, Antonio Di Grazia, Rami Dwairi, Alfredo Colantoni, Angela Ortenzi, Carmine Stolfi, Giovanni Monteleone
Metformin, a hypoglycemic drug used for treatment of type 2 diabetes, regulates also inflammatory pathways. By using several models of intestinal inflammation, we examined whether metformin exerts anti-inflammatory effects and investigated the basic mechanism by which metformin blocks pathologic signals. Colitic mice given metformin exhibited less colonic inflammation and increased expression of active AMP-activated protein kinase, a mediator of the metabolic effects of metformin, in both epithelial and lamina propria compartments...
March 14, 2018: Clinical Science (1979-)
Takeshi Akama, Tae-Hwa Chun
The visceral (VIS) and subcutaneous (SQ) fat pads are developmentally distinct white adipose tissue depots and contribute differently to inflammation and insulin resistance associated with obesity. The basic helix-loop-helix transcriptional regulator transcription factor 21 (TCF21) is a marker gene for white adipose tissues and is abundantly expressed in VIS-derived adipose stem cells (ASCs), but not in SQ-derived ASCs. However, TCF21's role in regulating fat depot-specific gene expression and function is incompletely understood...
March 14, 2018: Journal of Biological Chemistry
Yu-Ju Peng, Tang-Long Shen, Yu-Shan Chen, Harry John Mersmann, Bing-Hsien Liu, Shih-Torng Ding
BACKGROUND: Adiponectin (ADN) is an adipokine derived from adipocytes. It binds to adiponectin receptor 1 and 2 (AdipoR1 and R2) to exert its function in regulating whole-body energy homeostasis and inflammatory responses. However, the role of ADN-AdipoR1 signaling in intestinal inflammation is controversial, and its role in the regulation of neutrophils is still unclear. Our goal was to clarify the role of AdipoR1 signaling in colitis and the effects on neutrophils. METHODS: We generated porcine AdipoR1 transgenic mice (pAdipoR1 mice) and induced murine colitis using dextran sulfate sodium (DSS) to study the potential role of AdipoR1 in inflammatory bowel disease...
March 14, 2018: Journal of Biomedical Science
Marc Sorel, Jacques-Christian Beatrix, Blanche Locko, Catherine Armessen, Anne-Marie Domec, Otilia Lecompte, Sofiane Boucheneb, Benoit Harache, Jacques Robert, Jean-Pascal Lefaucheur
OBJECTIVES: The efficacy of ketamine in relieving complex regional pain syndrome (CRPS) lacks predictive factors. The value of three-phase bone scintigraphy (TPBS) was assessed or this purpose. METHODS: TPBS was performed in 105 patients with unilateral, focal CRPS of type 1 before 5 days of ketamine infusions. Tracer uptake was measured in the region of interest concerned by CRPS and the contralateral homologous region. For the three scintigraphic phases (vascular, tissular, and bone phases), an asymmetry ratio of fixation was calculated between the affected and the unaffected sides (VPr, TPr, and BPr)...
March 13, 2018: Clinical Journal of Pain
Muneeb U Rehman, Shahzada Mudasir Rashid, Saiema Rasool, Sheeba Shakeel, Bilal Ahmad, Sheikh Bilal Ahmad, Hassan Madkhali, Majid Ahmad Ganaie, Sabiya Majid, Showkat Ahmad Bhat
Development of diabetic nephropathy (DN) is directly linked to oxidative stress and inflammation. In this context, inflammatory and oxidative markers have gained much attention as targets for therapeutic intervention. We studied the effect of zingerone in a streptozotocin/high fat diet (STZ/HFD)-induced type 2 diabetic Wistar rat model. Zingerone also known as vanillyl acetone is a pharmacologically active compound present usually in dry ginger. STZ/HFD caused excessive increase in ROS and inflammation in experimental animals...
March 14, 2018: Archives of Physiology and Biochemistry
István Z Bátai, Ádám Horváth, Erika Pintér, Zsuzsanna Helyes, Gábor Pozsgai
Transient receptor potential ankyrin 1 (TRPA1) non-selective ligand-gated cation channels are mostly expressed in primary sensory neurons. Polysulfides (POLYs) are Janus-faced substances interacting with numerous target proteins and associated with both protective and detrimental processes. Activation of TRPA1 in sensory neurons, consequent somatostatin (SOM) liberation and action on sst4 receptors have recently emerged as mediators of the antinociceptive effect of organic trisulfide dimethyl trisulfide (DMTS)...
2018: Frontiers in Endocrinology
Pooja Sadana, Rebecca Geyer, Joern Pezoldt, Saskia Helmsing, Jochen Huehn, Michael Hust, Petra Dersch, Andrea Scrima
Yersinia pseudotuberculosis is a Gram-negative bacterium and zoonotic pathogen responsible for a wide range of diseases, ranging from mild diarrhea, enterocolitis, lymphatic adenitis to persistent local inflammation. The Y. pseudotuberculosis invasin D (InvD) molecule belongs to the invasin (InvA)-type autotransporter proteins, but its structure and function remain unknown. In this study, we present the first crystal structure of InvD, analyzed its expression and function in a murine infection model, and identified its target molecule in the host...
March 13, 2018: Journal of Biological Chemistry
Lois Salter, Amaka C Offiah, Nicholas Bishop
BACKGROUND: Elevated platelet counts are observed in cancer, autoimmunity and inflammation with concurrent illness. Proinflammatory cytokines are elevated in murine osteogenesis imperfecta (OI) models. We hypothesised that platelet counts might be elevated in children with moderate-severe OI. METHODS: We reviewed the hospital records of 71 children with moderate-severe OI, treated in the Sheffield Children's Hospital's Severe, Complex and Atypical Osteogenesis Imperfecta Highly Specialised Service...
March 13, 2018: Archives of Disease in Childhood
Bingqing Xie, Bharathi Laxman, Somaye Hashemifar, Randi Stern, T Conrad Gilliam, Natalia Maltsev, Steven R White
Basal airway epithelial cells (AEC) constitute stem/progenitor cells within the central airways and respond to mucosal injury in an ordered sequence of spreading, migration, proliferation, and differentiation to needed cell types. However, dynamic gene transcription in the early events after mucosal injury has not been studied in AEC. We examined gene expression using microarrays following mechanical injury (MI) in primary human AEC grown in submersion culture to generate basal cells and in the air-liquid interface to generate differentiated AEC (dAEC) that include goblet and ciliated cells...
2018: PloS One
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