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Matthew C Altman, Elizabeth Whalen, Alkis Togias, George T O'Connor, Leonard B Bacharier, Gordon R Bloomberg, Meyer Kattan, Robert A Wood, Scott Presnell, Petra LeBeau, Katy Jaffee, Cynthia M Visness, William W Busse, James E Gern
BACKGROUND: Childhood asthma in inner city populations is a major public health burden and understanding early life immune mechanisms that promote asthma onset is key to disease prevention. Children who develop asthma demonstrate a high prevalence of aeroallergen sensitization and T helper 2 (Th2)-type inflammation, however the early life immune events that lead to Th2 skewing and disease development are unknown. OBJECTIVE: We sought to use RNA sequencing of peripheral blood mononuclear cells (PBMCs) collected at age 2 to determine networks of immune responses that occur in children who develop allergy and asthma...
March 5, 2018: Journal of Allergy and Clinical Immunology
Kazuhiko Matsuo, Daisuke Nagakubo, Yuhei Komori, Shun Fujisato, Natsumi Takeda, Mizuki Kitamatsu, Keiji Nishiwaki, Ying-Shu Quan, Fumio Kamiyama, Naoki Oiso, Akira Kawada, Osamu Yoshie, Takashi Nakayama
Atopic dermatitis (AD) is a chronic inflammatory skin disease involving Th2 cells, eosinophils, and mast cells. Although CCR4 is a major chemokine receptor expressed on Th2 cells and regarded as a potential therapeutic target for allergic diseases, its role in AD still remains unclear. Here, by using a hydrogel patch as a transcutaneous delivery device for ovalbumin (an antigen) and Staphylococcus aureus δ-toxin (a mast cell activator), we efficiently induced acute AD-like skin lesions in BALB/c mice, a strain prone to Th2 responses, that were characterized by (1) increased numbers of eosinophils, mast cells, and CCR4-expressing Th2 cells in the skin lesions, (2) elevated levels of total and ovalbumin-specific IgE in the sera, and (3) increased expression of IL-4, IL-17A, IL-22, CCL17, CCL22, and CCR4 in the skin lesions...
March 3, 2018: Journal of Investigative Dermatology
Nick Vandeghinste, Jürgen Klattig, Catherine Jagerschmidt, Stéphanie Lavazais, Florence Marsais, Jan D Haas, Marielle Auberval, Felix Lauffer, Tara Moran, Mate Ongenaert, Maarten Van Balen, Sonia Dupont, Liên Lepescheux, Teresa Garcia, Stefan Härtle, Kilian Eyerich, Padraic G Fallon, Reginald Brys, Stefan Steidl
Interleukin-17C (IL-17C) is a functionally distinct member of the IL-17 family that was implicated to play a role in the pathogenesis of psoriasis. Here we confirmed that IL-17C is involved in psoriasis and explored potential roles for IL-17C in atopic dermatitis (AD). An anti-IL-17C antibody, MOR106, was generated that potently and selectively binds to human and mouse IL-17C, thereby inhibiting the binding of IL-17C to its IL-17RE receptor. The antibody inhibited cutaneous inflammation in an IL-23-induced psoriatic-like skin inflammation model...
February 20, 2018: Journal of Investigative Dermatology
Remo Castro Russo, Benedetta Savino, Massimiliano Mirolo, Chiara Buracchi, Giovanni Germano, Achille Anselmo, Luca Zammataro, Fabio Pasqualini, Alberto Mantovani, Massimo Locati, Mauro M Teixeira
RATIONALE: Chemokines coordinate lung inflammation and fibrosis by acting on chemokine receptors expressed on leukocytes and other cell types. Atypical chemokine receptors (ACKRs) bind, internalize and degrade chemokines, tuning homeostasis and immune responses. ACKR2 recognizes and decreases levels of inflammatory CC chemokines. The role of ACKR2 in fibrogenesis is unknown. OBJECTIVE: Investigate the role of ACKR2 in the context of pulmonary fibrosis. METHODS: The effects of ACKR2 expression and deficiency during inflammation and fibrosis were analyzed using a bleomycin-model of fibrosis, ACKR2-deficient mice, bone marrow chimeras and antibody-mediated leukocyte depletion...
February 22, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Daniela Schwotzer, Monika Niehof, Dirk Schaudien, Heiko Kock, Tanja Hansen, Clemens Dasenbrock, Otto Creutzenberg
BACKGROUND: Understanding the molecular mechanisms of nanomaterial interacting with cellular systems is important for appropriate risk assessment. The identification of early biomarkers for potential (sub-)chronic effects of nanoparticles provides a promising approach towards cost-intensive and animal consuming long-term studies. As part of a 90-day inhalation toxicity study with CeO2 NM-212 and BaSO4 NM-220 the present investigations on gene expression and immunohistochemistry should reveal details on underlying mechanisms of pulmonary effects...
February 20, 2018: Journal of Nanobiotechnology
Tae-Dong Jung, Sun-Il Choi, Seung-Hyun Choi, Bong-Yeon Cho, Wan-Sup Sim, Sang Jong Lee, Seon Ju Park, Dan-Bi Kim, Young-Cheul Kim, Jin-Ha Lee, Ok-Hwan Lee
Sesame is an important oilseed crop, which has been used as a traditional health food to ameliorate the prevention of various diseases. We evaluated the changes in the anti-allergic activities of sesame by bioconversion. SDS-PAGE of non-fermented sesame proteins showed major allergen bands, while that of fermented sesame showed only a few protein bands. Additionally, we investigated the effectiveness of fermented sesame by bioconversion in tumor necrosis factor-α (TNF-α)- and interferon-γ (IFN-γ)-induced HaCaT cells...
February 14, 2018: Nutrients
Eleonora Cremonesi, Valeria Governa, Jesus Francisco Glaus Garzon, Valentina Mele, Francesca Amicarella, Manuele Giuseppe Muraro, Emanuele Trella, Virginie Galati-Fournier, Daniel Oertli, Silvio Raffael Däster, Raoul A Droeser, Benjamin Weixler, Martin Bolli, Raffaele Rosso, Ulrich Nitsche, Nina Khanna, Adrian Egli, Simone Keck, Julia Slotta-Huspenina, Luigi M Terracciano, Paul Zajac, Giulio Cesare Spagnoli, Serenella Eppenberger-Castori, Klaus-Peter Janssen, Lubor Borsig, Giandomenica Iezzi
OBJECTIVE: Tumour-infiltrating lymphocytes (TILs) favour survival in human colorectal cancer (CRC). Chemotactic factors underlying their recruitment remain undefined. We investigated chemokines attracting T cells into human CRCs, their cellular sources and microenvironmental triggers. DESIGN: Expression of genes encoding immune cell markers, chemokines and bacterial 16S ribosomal RNA (16SrRNA) was assessed by quantitative reverse transcription-PCR in fresh CRC samples and corresponding tumour-free tissues...
February 6, 2018: Gut
Curtis J Perry, Andrés R Muñoz-Rojas, Katrina M Meeth, Laura N Kellman, Robert A Amezquita, Durga Thakral, Victor Y Du, Jake Xiao Wang, William Damsky, Alexandra L Kuhlmann, Joel W Sher, Marcus Bosenberg, Kathryn Miller-Jensen, Susan M Kaech
Eliciting effective antitumor immune responses in patients who fail checkpoint inhibitor therapy is a critical challenge in cancer immunotherapy, and in such patients, tumor-associated myeloid cells and macrophages (TAMs) are promising therapeutic targets. We demonstrate in an autochthonous, poorly immunogenic mouse model of melanoma that combination therapy with an agonistic anti-CD40 mAb and CSF-1R inhibitor potently suppressed tumor growth. Microwell assays to measure multiplex protein secretion by single cells identified that untreated tumors have distinct TAM subpopulations secreting MMP9 or cosecreting CCL17/22, characteristic of an M2-like state...
February 7, 2018: Journal of Experimental Medicine
Marta Epeldegui, Larry Magpantay, Yu Guo, Gordana Halec, William G Cumberland, Priscilla K Yen, Bernard Macatangay, Joseph B Margolick, Anne F Rositch, Steven Wolinsky, Otoniel Martinez-Maza, Shehnaz K Hussain
: Chronic immune activation is a harbinger of AIDS-associated non-Hodgkin lymphoma (AIDS-NHL), yet the underlying basis is unclear. Microbial translocation, the passage of microbial components from the gastrointestinal tract into the systemic circulation, is a source of systemic immune activation in HIV infection and may be an important contributor to the chronic B-cell activation and subsequent AIDS-NHL development. We measured biomarkers of microbial translocation including bacterial receptors/antibodies, intestinal barrier proteins, and macrophage activation-associated cytokines/chemokines, in serum from 200 HIV-infected men from the Multicenter AIDS Cohort Study prior to their AIDS-NHL diagnosis (mean = 3...
February 8, 2018: AIDS
Alexandr Karpov, Anna Rvacheva, Maryana Shogenova, Radima Merova, Vladimir Naumov, Masenko Valerij
No abstract text is available yet for this article.
August 2017: Atherosclerosis
Sonia Boulakirba, Anja Pfeifer, Rana Mhaidly, Sandrine Obba, Michael Goulard, Thomas Schmitt, Paul Chaintreuil, Anne Calleja, Nathan Furstoss, François Orange, Sandra Lacas-Gervais, Laurent Boyer, Sandrine Marchetti, Els Verhoeyen, Frederic Luciano, Guillaume Robert, Patrick Auberger, Arnaud Jacquel
CSF-1 and IL-34 share the CSF-1 receptor and no differences have been reported in the signaling pathways triggered by both ligands in human monocytes. IL-34 promotes the differentiation and survival of monocytes, macrophages and osteoclasts, as CSF-1 does. However, IL-34 binds other receptors, suggesting that differences exist in the effect of both cytokines. In the present study, we compared the differentiation and polarization abilities of human primary monocytes in response to CSF-1 or IL-34. CSF-1R engagement by one or the other ligands leads to AKT and caspase activation and autophagy induction through expression and activation of AMPK and ULK1...
January 10, 2018: Scientific Reports
Laura Hesse, Nienke van Ieperen, Corine Habraken, Arjen H Petersen, Silvia Korn, Tim Smilda, Betty Goedewaagen, Marcel H Ruiters, Adrianus C van der Graaf, Martijn C Nawijn
Allergen-specific immunotherapy can induce long-term suppression of allergic symptoms, reduce medication use and prevent exacerbations of allergic rhinitis and asthma. Current treatment is based on crude allergen extracts, which contain immunostimulatory components such as β-glucans, chitins and endotoxin. Use of purified or recombinant allergens might therefore increase efficacy of treatment. Here, we test application of purified natural group 1 and 2 allergens from Dermatophagoides pteronyssinus (Der p) for subcutaneous immunotherapy (SCIT) treatment in a house dust mite (HDM) driven mouse model of allergic asthma...
January 10, 2018: Allergy
E Scott Halstead, Todd M Umstead, Michael L Davies, Yuka Imamura Kawasawa, Patricia Silveyra, Judie Howyrlak, Linlin Yang, Weichao Guo, Sanmei Hu, Eranda Kurundu Hewage, Zissis C Chroneos
BACKGROUND: Influenza A viruses cause life-threatening pneumonia and lung injury in the lower respiratory tract. Application of high GM-CSF levels prior to infection has been shown to reduce morbidity and mortality from pathogenic influenza infection in mice, but the mechanisms of protection and treatment efficacy have not been established. METHODS: Mice were infected intranasally with influenza A virus (PR8 strain). Supra-physiologic levels of GM-CSF were induced in the airways using the double transgenic GM-CSF (DTGM) or littermate control mice starting on 3 days post-infection (dpi)...
January 5, 2018: Respiratory Research
Maryam Nakhaei-Nejad, David Barilla, Chieh-Hsin Lee, Gregg Blevins, Fabrizio Giuliani
Objective: Lymphopenia is a common occurrence of disease-modifying therapies (DMTs) for relapsing-remitting MS (RRMS). The aim of this study was to dissect the prevalence of various lymphocyte subsets in patients with RRMS treated with 2 DMTs commonly associated with lymphopenia, dimethyl fumarate (DMF), and fingolimod (FTY). Methods: Multicolor flow cytometry and multiplex assays were used to identify up to 50 lymphocyte subpopulations and to examine the expression of multiple cytokines in selected patients...
March 2018: Neurology® Neuroimmunology & Neuroinflammation
Ivana M Lalić, Rudolf Bichele, Anja Repar, Sanja Z Despotović, Saša Petričević, Martti Laan, Pärt Peterson, Jürgen Westermann, Živana Milićević, Ivana Mirkov, Novica M Milićević
It is well known that bacterial lipopolysaccharide (LPS) induces migration of several cellular populations within the spleen. However, there are no data about the impact of LPS on B and T lymphocytes present in the red pulp. Therefore, we used an experimental model in which we tested the effects of intravenously injected LPS on the molecular, cellular and structural changes of the spleen, with special reference to the red pulp lymphocytes. We discovered that LPS induced a massive relocation of B and T lymphocytes from the splenic red pulp, which was independent of the tumor necrosis factor receptor-1 signaling axis...
December 28, 2017: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
Xin Zhang, Jing Zheng, Li Zhang, Ying Liu, Gai Ping Chen, Hong Ping Zhang, Lei Wang, De Ying Kang, Lisa G Wood, Gang Wang
BACKGROUND: Obesity negatively impacts asthma control, but the inflammatory mechanisms are poorly understood. OBJECTIVE: To explore which systemic inflammatory mediators mediate the effects of obesity on asthma control. METHODS: The subjects with stable asthma (n = 108) underwent assessment of clinical characteristics, which included using The Asthma Control Questionnaire (ACQ)-6. Obesity was defined as a body mass index (BMI) of ≥30 kg/m2, overweight was defined as BMI between 25 to 29...
January 2, 2018: Allergy and Asthma Proceedings:
Li-Rong Yu, Zhijun Cao, Issam Makhoul, Jaclyn R Daniels, Suzanne Klimberg, Jeanne Y Wei, Jane Pf Bai, Jinong Li, Julia T Lathrop, Richard D Beger, Valentina K Todorova
Cancer treatment with doxorubicin (DOX) can induce cumulative dose-dependent cardiotoxicity. Currently, there are no specific biomarkers that can identify patients at risk during the initial doses of chemotherapy. The aim of this study was to examine plasma cytokines/chemokines and potential cardiovascular biomarkers for the prediction of DOX-induced cardiotoxicity. Plasma samples were collected before (T0), and after the first (T1) and the second (T2) cycles of DOX-based chemotherapy of 27 breast cancer patients, including five patients who presented with >10% decline of left ventricular ejection fraction (LVEF), five patients with LVEF decline of 5-10%, and 17 patients who maintained normal LVEF at the end of chemotherapy (240 mg/m2 cumulative dose of DOX from four cycles of treatment)...
February 2018: Experimental Biology and Medicine
Hye-Sun Lim, Sae-Rom Yo, Mee-Young Lee, Chang-Seob Seo, Hyeun-Kyoo Shin, Soo-Jin Jeong
Inflammatory skin disease are caused by multiple factors, including susceptibility genes, and immunologic and environmental factors, and are characterized by an increase in epidermal thickness and the infiltration of macrophages, keratinocytes, mast cells, eosinophils and other inflammatory cells. Keratinocytes may serve an important role in the pathogenesis of inflammatory skin diseases. The traditional herbal decoction Hyangso‑san (HSS) has been used to treat symptoms of the common cold, including headache, pantalgia, fever and chills...
February 2018: Molecular Medicine Reports
Gang Geng, Ying Du, Jihong Dai, Daiyin Tian, Yunqiu Xia, Zhou Fu
BACKGROUND: KIF3A expression was decreased in asthmatic child patients and animal. Impaired KIF3A expression resulted in increased Th2 inflammation in mice and apoptosis in renal tubular epithelium and photoreceptor cells. This work aimed to investigate the role of KIF3A in epithelium apoptosis and bronchial inflammation in asthma. METHODS: After establishment of ovalbumin induced asthma, the mice were infected with KIF3A adenovirus through nasal cavity inhalation...
November 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Mazène Hochane, Denis Raison, Catherine Coquard, Claire Béraud, Audrey Bethry, Sabrina Danilin, Thierry Massfelder, Mariette Barthelmebs
Mesangial cell (MC) injury is a prominent feature of glomerulonephritis. Activated MC secretes inflammatory mediators which induce cell apoptosis. Parathyroid hormone-related peptide (PTHrP) is a locally active cytokine that enhances cell survival and is upregulated by pro-inflammatory factors in many cell types. The aim of this study was to analyze the regulation of PTHrP expression by inflammatory cytokines, and to evaluate whether PTHrP itself acts as a pro-inflammatory and/or survival factor on male murine MC in primary culture...
November 15, 2017: American Journal of Physiology. Cell Physiology
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