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https://www.readbyqxmd.com/read/28917668/gut-microbe-mediated-suppression-of-inflammation-associated-colon-carcinogenesis-by-luminal-histamine-production
#1
Chunxu Gao, Bhanu Priya Ganesh, Zhongcheng Shi, Rajesh Rasik Shah, Robert Fultz, Angela Major, Susan Venable, Monica Lugo, Kathleen Hoch, Xiaowei Chen, Anthony Haag, Timothy C Wang, James Versalovic
Microbiome-mediated suppression of carcinogenesis may open new avenues for identification of therapeutic targets and prevention strategies in oncology. Histidine decarboxylase (HDC) deficiency has been shown to promote inflammation-associated colorectal cancer by accumulation of CD11b(+)Gr-1(+) immature myeloid cells, indicating a potential antitumorigenic effect of histamine. Here, we demonstrate that administration of hdc(+)Lactobacillus reuteri in the gut resulted in luminal hdc gene expression and histamine production in the intestines of Hdc(-/-) mice...
September 6, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28842466/il-18-drives-ilc3-proliferation-and-promotes-il-22-production-via-nf-%C3%AE%C2%BAb
#2
Aaron R Victor, Ansel P Nalin, Wenjuan Dong, Susan McClory, Min Wei, Charlene Mao, Raleigh D Kladney, Youssef Youssef, Wing Keung Chan, Edward L Briercheck, Tiffany Hughes, Steven D Scoville, Jason R Pitarresi, Charlie Chen, Sarah Manz, Lai-Chu Wu, Jianying Zhang, Michael C Ostrowski, Aharon G Freud, Gustavo W Leone, Michael A Caligiuri, Jianhua Yu
Group 3 innate lymphoid cells (ILC3s) are important regulators of the immune system, maintaining homeostasis in the presence of commensal bacteria, but activating immune defenses in response to microbial pathogens. ILC3s are a robust source of IL-22, a cytokine critical for stimulating the antimicrobial response. We sought to identify cytokines that can promote proliferation and induce or maintain IL-22 production by ILC3s and determine a molecular mechanism for this process. We identified IL-18 as a cytokine that cooperates with an ILC3 survival factor, IL-15, to induce proliferation of human ILC3s, as well as induce and maintain IL-22 production...
August 25, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28827067/increased-tryptophan-metabolism-is-associated-with-activity-of-inflammatory-bowel-diseases
#3
Susanna Nikolaus, Berenice Schulte, Natalie Al-Massad, Florian Thieme, Dominik M Schulte, Johannes Bethge, Ateequr Rehman, Florian Tran, Konrad Aden, Robert Häsler, Natalie Moll, Gregor Schütze, Markus J Schwarz, Georg H Waetzig, Philip Rosenstiel, Michael Krawczak, Silke Szymczak, Stefan Schreiber
BACKGROUND & AIMS: Administration of tryptophan, and some of its metabolites, reduces the severity of colitis in mice, whereas removing tryptophan from the diet increases susceptibility to colitis. Transfer of the intestinal microbiome can increase susceptibility of mice to colitis. We aimed to systematically evaluate serum levels of tryptophan and its metabolites in patients with inflammatory bowel diseases (IBD), and study their association with clinical and serologic features. METHODS: We studied 535 consecutive patients with IBD (211 with ulcerative colitis [UC], 234 with Crohn's disease [CD]; 236 male), enrolled in Germany from August 2013 through April 2014 and followed until July 2016...
August 18, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28806280/integrated-analysis-of-biopsies-from-inflammatory-bowel-disease-patients-identifies-saa1-as-a-link-between-mucosal-microbes-with-th17-and-th22-cells
#4
Mei San Tang, Rowann Bowcutt, Jacqueline M Leung, Martin J Wolff, Uma M Gundra, David Hudesman, Lisa B Malter, Michael A Poles, Lea Ann Chen, Zhiheng Pei, Antonio G Neto, Wasif M Abidi, Thomas Ullman, Lloyd Mayer, Richard A Bonneau, Ilseung Cho, Pʼng Loke
BACKGROUND: Inflammatory bowel diseases (IBD) are believed to be driven by dysregulated interactions between the host and the gut microbiota. Our goal is to characterize and infer relationships between mucosal T cells, the host tissue environment, and microbial communities in patients with IBD who will serve as basis for mechanistic studies on human IBD. METHODS: We characterized mucosal CD4 T cells using flow cytometry, along with matching mucosal global gene expression and microbial communities data from 35 pinch biopsy samples from patients with IBD...
September 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28736556/ras-signaling-inhibitors-attenuate-disease-in-adjuvant-induced-arthritis-via-targeting-pathogenic-antigen-specific-th17-type-cells
#5
Morad Zayoud, Victoria Marcu-Malina, Einav Vax, Jasmine Jacob-Hirsch, Galit Elad-Sfadia, Iris Barshack, Yoel Kloog, Itamar Goldstein
The Ras family of GTPases plays an important role in signaling nodes downstream to T cell receptor and CD28 activation, potentially lowering the threshold for T-cell receptor activation by autoantigens. Somatic mutation in NRAS or KRAS may cause a rare autoimmune disorder coupled with abnormal expansion of lymphocytes. T cells from rheumatoid arthritis (RA) patients show excessive activation of Ras/MEK/ERK pathway. The small molecule farnesylthiosalicylic acid (FTS) interferes with the interaction between Ras GTPases and their prenyl-binding chaperones to inhibit proper plasma membrane localization...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28706520/hypothermia-promotes-interleukin-22-expression-and-fine-tunes-its-biological-activity
#6
Evgeny Chichelnitskiy, Britta Himmelseher, Malte Bachmann, Josef Pfeilschifter, Heiko Mühl
Disturbed homeostasis as a result of tissue stress can provoke leukocyte responses enabling recovery. Since mild hypothermia displays specific clinically relevant tissue-protective properties and interleukin (IL)-22 promotes healing at host/environment interfaces, effects of lowered ambient temperature on IL-22 were studied. We demonstrate that a 5-h exposure of endotoxemic mice to 4°C reduces body temperature by 5.0° and enhances splenic and colonic il22 gene expression. In contrast, tumor necrosis factor-α and IL-17A were not increased...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28697061/elevation-of-circulating-th17-th22-cells-exposed-to-low-level-formaldehyde-and-its-relevance-to-formaldehyde-induced-occupational-allergic-contact-dermatitis
#7
Weihua Mai, Xingwei Liu, Guangxiao Su, Wenying Zhou, Ziping Wen, Dongqing Lu
OBJECTIVES: The aim of this study was to investigate the effects of formaldehyde exposure on Th17 and Th22 cells and its relevance to human occupational allergic contact dermatitis (OACD). METHODS: Circulating IL17-/IL22-secreting cells and serum IL17/IL22 levels in formaldehyde-exposed workers at Occupational Exposure Limit and nonexposed controls were assessed. RESULTS: The IL17 and IL22 cell population were detected in both CD3CD8 and CD3CD8 cells...
July 10, 2017: Journal of Occupational and Environmental Medicine
https://www.readbyqxmd.com/read/28611056/igf1-potentiates-the-pro-inflammatory-response-in-human-peripheral-blood-mononuclear-cells-via-mapk
#8
Thalijn Liliana Catharina Wolters, Mihai Gheorghe Netea, Ad R Hermus, Jan Wa Smit, Romana T Netea-Maier
Introduction: Acromegaly is characterized by growth hormone (GH) and Insulin-like Growth Factor 1 (IGF1) excess and is accompanied by an increased cardiovascular diseases (CVD) risk. As innate immune responses are crucial in CVD development, and IGF1 is linked to subclinical inflammation, we hypothesized that GH/IGF1 excess contributes to CVD development via potentiating systemic inflammation. We aimed to assess the effects of GH/IGF1 on inflammatory cytokine production. Methods: Whole blood from acromegaly patients and healthy volunteers, and peripheral blood mononuclear cells (PBMC) from healthy volunteers were stimulated with Toll-like receptor (TLR) ligands, with or without adding GH or IGF1 (in PBMC)...
June 13, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28526849/interleukin-22-attenuated-angiotensin-ii-induced-acute-lung-injury-through-inhibiting-the-apoptosis-of-pulmonary-microvascular-endothelial-cells
#9
Zhiyong Wu, Zhipeng Hu, Xin Cai, Wei Ren, Feifeng Dai, Huagang Liu, Jinxing Chang, Bowen Li
Apoptosis of pulmonary microvascular endothelial cells (PMVECs) was considered to be closely related to the pathogenesis of acute lung injury (ALI). We aim to investigate whether IL-22 plays protective roles in lung injury through inhibiting the apoptosis of PMVECs. ALI model was induced through subcutaneous infusion of angiotensin II (Ang II). Lung injury and infiltration of inflammatory cells were evaluated by determining the PaO2/FiO2, calculation of dry to weight ratio in lung, and immunohistochemisty analysis...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28506283/prolactin-blocks-the-expression-of-receptor-activator-of-nuclear-factor-%C3%AE%C2%BAb-ligand-and-reduces-osteoclastogenesis-and-bone-loss-in-murine-inflammatory-arthritis
#10
Maria G Ledesma-Colunga, Norma Adán, Georgina Ortiz, Mariana Solís-Gutiérrez, Fernando López-Barrera, Gonzalo Martínez de la Escalera, Carmen Clapp
BACKGROUND: Prolactin (PRL) reduces joint inflammation, pannus formation, and bone destruction in rats with polyarticular adjuvant-induced arthritis (AIA). Here, we investigate the mechanism of PRL protection against bone loss in AIA and in monoarticular AIA (MAIA). METHODS: Joint inflammation, trabecular bone loss, and osteoclastogenesis were evaluated in rats with AIA treated with PRL (via osmotic minipumps) and in mice with MAIA that were null (Prlr-/-) or not (Prlr+/+) for the PRL receptor...
May 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28487695/regulatory-t-cells-and-pro-inflammatory-responses-predominate-in-children-with-tuberculosis
#11
Elizabeth Whittaker, Mark Nicol, Heather J Zar, Beate Kampmann
BACKGROUND: Following infection with Mycobacterium tuberculosis (M.tb), children are more susceptible to develop disease particularly extrapulmonary disease than adults. The exact mechanisms required for containment of M.tb are not known, but would be important to identify correlates of protection. OBJECTIVE: To comprehensively analyze key immune responses to mycobacteria between HIV-negative children with extrapulmonary TB (EPTB) compared to children with pulmonary TB (PTB) or healthy controls...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28406748/radiation-induced-dermatitis-is-mediated-by-il17-expressing-%C3%AE-%C3%AE-t-cells
#12
Wupeng Liao, Tom K Hei, Simon K Cheng
Radiation dermatitis is a serious cutaneous injury caused by radiation therapy or upon accidental nuclear exposure. However, the pathogenic immune mechanisms underlying this injury are still poorly understood. We seek to discover how the dysregulated immune response after irradiation orchestrates skin inflammation. The skin on the left flank of C57BL/6J wild-type and C57BL/6J Tcrd(-/-) mice, which are deficit in γδ T cells, was exposed to a single X-ray dose of 25 Gy, and the right-flank skin was used as a sham-irradiated control...
April 2017: Radiation Research
https://www.readbyqxmd.com/read/28390867/efficacy-and-safety-of-medi2070-an-antibody-against-interleukin-23-in-patients-with-moderate-to-severe-crohn-s-disease-a-phase-2a-study
#13
RANDOMIZED CONTROLLED TRIAL
Bruce E Sands, Jingjing Chen, Brian G Feagan, Mark Penney, William A Rees, Silvio Danese, Peter D R Higgins, Paul Newbold, Raffaella Faggioni, Kaushik Patra, Jing Li, Paul Klekotka, Chris Morehouse, Erik Pulkstenis, Jörn Drappa, René van der Merwe, Robert A Gasser
BACKGROUND & AIMS: MEDI2070 is a human monoclonal antibody that selectively inhibits interleukin 23 (IL23), a cytokine implicated in the pathogenesis of Crohn's disease (CD). We analyzed its safety and efficacy in treatment of CD in a phase 2a study. METHODS: We conducted a double-blind, placebo-controlled study of 119 adults with moderate to severe CD failed by treatment with tumor necrosis factor antagonists. Patients were randomly assigned (1:1) to groups given MEDI2070 (700 mg) or placebo intravenously at weeks 0 and 4...
July 2017: Gastroenterology
https://www.readbyqxmd.com/read/28296821/protease-activated-receptor-1-plays-a-proinflammatory-role-in-colitis-by-promoting-th17-related-immunity
#14
Muhammad A Saeed, Garrett Z Ng, Jan Däbritz, Josef Wagner, Louise Judd, Jia-Xi Han, Poshmaal Dhar, Carl D Kirkwood, Philip Sutton
BACKGROUND: Proteolytic cleavage of protease-activated receptor 1 (PAR1) can result in potent downstream regulatory effects on inflammation. Although PAR1 is expressed throughout the gastrointestinal tract and activating proteases are increased in inflammatory bowel disease, the effect of PAR1 activation on colitis remains poorly understood, and has not previously been studied in pediatric disease. METHODS: Expression of PAR1 and inflammatory cytokines in colonic biopsies from pediatric patients with Crohn's disease exhibiting active moderate to severe colitis was measured by quantitative PCR...
April 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28286877/il-22-controls-iron-dependent-nutritional-immunity-against-systemic-bacterial-infections
#15
Kei Sakamoto, Yun-Gi Kim, Hideki Hara, Nobuhiko Kamada, Gustavo Caballero-Flores, Emanuela Tolosano, Miguel P Soares, José L Puente, Naohiro Inohara, Gabriel Núñez
Host immunity limits iron availability to pathogenic bacteria, but whether immunity limits pathogenic bacteria from accessing host heme, the major source of iron in the body, remains unclear. Using Citrobacter rodentium, a mouse enteric pathogen and Escherichia coli, a major cause of sepsis in humans as models, we find that interleukin-22, a cytokine best known for its ability to promote epithelial barrier function, also suppresses the systemic growth of bacteria by limiting iron availability to the pathogen...
February 2017: Science Immunology
https://www.readbyqxmd.com/read/28177259/radiation-induced-dermatitis-is-mediated-by-il17-expressing-%C3%AE-%C3%AE-t-cells
#16
Wupeng Liao, Tom K Hei, Simon K Cheng
Radiation dermatitis is a serious cutaneous injury caused by radiation therapy or upon accidental nuclear exposure. However, the pathogenic immune mechanisms underlying this injury are still poorly understood. We seek to discover how the dysregulated immune response after irradiation orchestrates skin inflammation. The skin on the left flank of C57BL/6J wild-type and C57BL/6J Tcrd(-/-) mice, which are deficit in γδ T cells, was exposed to a single X-ray dose of 25 Gy, and the right-flank skin was used as a sham-irradiated control...
February 8, 2017: Radiation Research
https://www.readbyqxmd.com/read/28172748/p356-treatment-with-anakinra-induces-t-cell-production-of-il22-and-gi-mucosal-healing-in-an-il-10ra-mutation-patient
#17
J Li, D Shouval, A Doty, S Snapper, S Glover
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28139719/a-functional-il22-polymorphism-rs2227473-is-associated-with-predisposition-to-childhood-cerebral-malaria
#18
Sandrine Marquet, Ianina Conte, Belco Poudiougou, Laurent Argiro, Hélia Dessein, Charlène Couturier, Florence Burté, Aboubacar A Oumar, Biobele J Brown, Abdoualye Traore, Nathaniel K Afolabi, Abdoulaye Barry, Samuel Omokhodion, Wuraola A Shokunbi, Olugbemiro Sodeinde, Ogobara Doumbo, Delmiro Fernandez-Reyes, Alain J Dessein
Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection. This encephalopathy is characterized by coma and is thought to result from mechanical microvessel obstruction and an excessive activation of immune cells leading to pathological inflammation and blood-brain barrier alterations. IL-22 contributes to both chronic inflammatory and infectious diseases, and may have protective or pathogenic effects, depending on the tissue and disease state. We evaluated whether polymorphisms (n = 46) of IL22 and IL22RA2 were associated with CM in children from Nigeria and Mali...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28115058/ccr6-is-dispensable-for-the-development-of%C3%A2-skin-lesions-induced-by-imiquimod-despite-its-effect-on-epidermal-homing-of%C3%A2-il-22-producing-cells
#19
Perrine M Cochez, Camille Michiels, Emilie Hendrickx, Nicolas Dauguet, Guy Warnier, Jean-Christophe Renauld, Laure Dumoutier
Expression of the chemokine receptor Ccr6 is shared by most IL-22-producing cells, and Ccr6-deficient mice showed decreased IL-22 production and skin inflammation upon IL-23 intradermal injections. To determine whether this observation might be extended to another psoriasis model, we applied imiquimod on Ccr6-deficient mice. Although epidermal IL-22 production was decreased because of a deficient recruitment of γδ T cells in these mice, they were not protected against psoriatic lesions. When primary epidermis or dermis tissue culture cells from nontreated mice were stimulated ex vivo with IL-1α/IL-2/IL-23, we observed that Ccr6 is crucial for Il22 expression from epidermal but not dermal cultures...
May 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27876571/fusobacterium-nucleatum-increases-proliferation-of-colorectal-cancer-cells-and-tumor-development-in-mice-by-activating-toll-like-receptor-4-signaling-to-nuclear-factor-%C3%AE%C2%BAb-and-up-regulating-expression-of-microrna-21
#20
Yongzhi Yang, Wenhao Weng, Junjie Peng, Leiming Hong, Lei Yang, Yuji Toiyama, Renyuan Gao, Minfeng Liu, Mingming Yin, Cheng Pan, Hao Li, Bomin Guo, Qingchao Zhu, Qing Wei, Mary-Pat Moyer, Ping Wang, Sanjun Cai, Ajay Goel, Huanlong Qin, Yanlei Ma
BACKGROUND & AIMS: Nearly 20% of the global cancer burden can be linked to infectious agents. Fusobacterium nucleatum promotes tumor formation by epithelial cells via unclear mechanisms. We aimed to identify microRNAs (miRNAs) induced by F nucleatum and evaluate their ability to promote colorectal carcinogenesis in mice. METHODS: Colorectal cancer (CRC) cell lines were incubated with F nucleatum or control reagents and analyzed in proliferation and would healing assays...
March 2017: Gastroenterology
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