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Britton Trabert, Ronald C Eldridge, Ruth M Pfeiffer, Meredith S Shiels, Troy J Kemp, Chantal Guillemette, Patricia Hartge, Mark E Sherman, Louise A Brinton, Amanda Black, Anil K Chaturvedi, Allan Hildesheim, Sonja I Berndt, Mahboobeh Safaeian, Ligia Pinto, Nicolas Wentzensen
Inflammation is proposed to increase risk of developing endometrial cancer, but few prospective epidemiologic studies have investigated the relationship between circulating inflammation markers and endometrial cancer risk. In a nested case-control study within the PLCO Screening Trial we measured serum levels of 64 inflammation-related biomarkers in 284 incident endometrial cancer cases and 284 matched controls. Using multivariable logistic regression inflammation markers were evaluated individually and combined into a cross-validated inflammation score...
October 22, 2016: International Journal of Cancer. Journal International du Cancer
Tamara V Smelaya, Olesya B Belopolskaya, Svetlana V Smirnova, Artem N Kuzovlev, Viktor V Moroz, Arkadiy M Golubev, Noel A Pabalan, Lyubov E Salnikova
The role of host genetic variation in pneumonia development and outcome is poorly understood. We studied common polymorphisms in the genes of proinflammatory cytokines (IL6 rs1800795, IL8 rs4073, IL1B rs16944), anti-inflammatory cytokines (IL10 rs1800896, IL4 rs2243250, IL13 rs20541) and toll-like receptors (TLR2 rs5743708 and rs4696480, TLR4 rs4986791, TLR9 rs352139, rs5743836 and rs187084) in patients with community-acquired pneumonia (CAP) (390 cases, 203 controls) and nosocomial pneumonia (355 cases, 216 controls)...
October 11, 2016: Scientific Reports
Nicola L D Overton, David W Denning, Paul Bowyer, Angela Simpson
BACKGROUND: In patients with asthma, the fungus Aspergillus fumigatus can cause allergic bronchopulmonary aspergillosis (ABPA). Familial ABPA is reported, and some genetic factors have been associated with the disease, however, these are small studies (n ≤ 38) and do not explain all cases of ABPA. METHODS: We analysed SNPs in 95 ABPA patients, comparing frequencies to 152 atopic asthmatic and 279 healthy controls. Twenty two genes were selected from literature, and 195 tagging SNPs were analysed for genetic association with ABPA using logistic regression corrected for multiple testing...
2016: Allergy, Asthma, and Clinical Immunology
Gen Li, Anqing Wu, Dandan Qi, Fengmei Cui, Yanan Zeng, Fang Xie, Hongya Wu, Yongping Gu, Qiu Chen, Xueguang Zhang
Immediate medical intervention is required after pelvic tumor radiotherapy to protect the radiosensitive intestine and also to mitigate tumor growth. Toll-like receptors (TLRs) have been shown to promote tissue repair processes. Here, we analyzed the effect observed upon combining the TLR2 agonist, peptidoglycan (PGN), with radiation therapy on tumors as well as intestinal tissue, both in vitro and in vivo. In contrast to radiotherapy alone, PGN when combined with ionizing radiation (IR) elicited enhanced antitumor effects and also reduced the IR-induced intestinal damage...
September 30, 2016: Oncotarget
Vanessa Popp, Katharina Gerlach, Stefanie Mott, Agnieszka Turowska, Holger Garn, Raja Atreya, Hans-Anton Lehr, I-Cheng Ho, Harald Renz, Benno Weigmann, Markus F Neurath
BACKGROUND & AIMS: GATA3 is a transcription factor that regulates T-cell production of cytokines. We investigated the role of GATA3 in development of colitis in mice. METHODS: We performed quantitative PCR and immunofluorescence analyses of colon tissues from patients with Crohn's disease (n= 61) or ulcerative colitis (UC, n= 74), or patients without inflammatory bowel diseases (n= 22), to measure levels of GATA3. Colitis was induced by administration of oxazolone or 2,4,6-Trinitrobenzenesulfonic acid (TNBS) to control mice, mice with T-cell specific deletion of GATA3, and mice with deletion of tumor necrosis factor receptor-1 (TNFR1) and TNFR2 (TNFR double knockouts); some mice were given a GATA3-specific DNAzyme (hgd40) or a control DNAzyme via intrarectal administration, or systemic injections of an antibody to TNF prior or during sensitization and challenge phase of colitis induction...
September 14, 2016: Gastroenterology
M Orciani, A Campanati, M Caffarini, G Ganzetti, V Consales, G Lucarini, A Offidani, R Di Primio
BACKGROUND: Atopic dermatitis (AD) is a chronic, and inflammatory disease characterized by a marked imbalance of Th2 versus Th1-Th17 in the early phase of AD, whereas a mixed Th1/Th2 pattern of inflammation is usually found at chronic stage. These features have not been extensively evaluated in undifferentiated skin cells of patients affected by atopic dermatitis (AD). OBJECTIVE: the relative expression of 22 genes encoding for Th1, Th2, and Th17 cytokines and the secretion of the corresponding proteins have been analyzed in Cutaneous Mesenchymal Stem Cells (MSCs) isolated from skin of AD patients (AD-MSCs) to evaluate their role on AD onset...
September 17, 2016: British Journal of Dermatology
Sefayet Karaca, Ersoy Civelek, Mehmet Karaca, Umit M Sahiner, Riza K Ozgul, Can N Kocabas, Renato Polimanti, Bülent E Sekerel
To dissect the role of immunogenetics in allergy and asthma, we performed a phenome-wide association study in 974 Turkish children selected from a cross-sectional study conducted using ISAAC (International Study of Asthma and Allergies in Children) Phase II tools. We investigated 9 loci involved in different immune functions (ADAM33, ADRB2, CD14, IL13, IL4, IL4R, MS4A2, SERPINE1, and TNF) with respect to 116 traits assessed through blood tests, hypertonic saline challenge tests, questionnaires, and skin prick tests...
2016: Scientific Reports
Tarcio Teodoro Braga, Matheus Correa-Costa, Hatylas Azevedo, Reinaldo Correia Silva, Mario Costa Cruz, Maira Estanislau Soares Almeida, Meire Ioshie Hiyane, Carlos Alberto Moreira-Filho, Marinilce Fagundes Santos, Katia Regina Perez, Iolanda Midea Cuccovia, Niels Olsen Saraiva Camara
INTRODUCTION: Macrophages are heterogeneous and thus can be correlated with distinct tissue outcomes after injury. Conflicting data have indicated that the M2-related phenotype directly triggers fibrosis. Conversely, we hypothesize here that the inflammatory milieu provided by early infiltration of pro-inflammatory macrophages dictates tissue scarring after injury. METHODS AND RESULTS: We first determined that tissue-localized macrophages exhibit a pro-inflammatory phenotype (p40IL12(+)CCR7(+)CD11b(+)) during the early phase of a chronic injury model, in contrast to a pro-resolving phenotype (Arg1(+)IL10(+)CD206(+)CD11b(+)) at a later stage...
September 2016: Immunity, Inflammation and Disease
Ramakrishna Edukulla, Kira Lee Rehn, Bo Liu, Jaclyn W McAlees, Gurjit K Hershey, Yui Hsi Wang, Ian Lewkowich, Andrew W Lindsley
INTRODUCTION: Ceramide is the central substrate of sphingolipid metabolism and plays a key role in cellular signal transduction pathways, regulating apoptosis, differentiation, and chemotaxis. Alterations in airway ceramide levels are observed in multiple pulmonary diseases and recent human genetic association studies have linked dysregulation of sphingolipid regulatory genes with asthma pathogenesis. METHODS: Utilizing myriocin, a potent inhibitor of sphingolipid synthesis, we evaluated the immune regulatory role of de novo ceramide generation in vitro and in vivo...
September 2016: Immunity, Inflammation and Disease
Shanieek Lawrence, Samuel T Pellom, Anil Shanker, Margaret M Whalen
Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo...
September 7, 2016: Journal of Immunotoxicology
Chiara Raggi, Margherita Correnti, Antonio Sica, Jesper B Andersen, Vincenzo Cardinale, Domenico Alvaro, Giovanna Chiorino, Elisa Forti, Shannon Glaser, Gianfranco Alpini, Annarita Destro, Francesca Sozio, Luca Di Tommaso, Massimo Roncalli, Jesus M Banales, Cédric Coulouarn, Luis Bujanda, Guido Torzilli, Pietro Invernizzi
BACKGROUND & AIMS: A therapeutically challenging subset of cells, termed cancer stem cells (CSCs) are responsible for cholangiocarcinoma (CCA) clinical severity. Presence of tumor-associated macrophages (TAMs) has prognostic significance in CCA and other malignancies. Thus, we hypothesized that CSCs may actively shape their tumor-supportive immune niche. METHODS: CCA cells were cultured in 3D conditions to generate spheres. CCA sphere analysis of in vivo tumorigenic-engraftment in immune-deficient mice and molecular characterization was performed...
September 1, 2016: Journal of Hepatology
Wei Zhang, Zi Wang, Yunping Luo, Dingrong Zhong, Yufeng Luo, Daobin Zhou
Peripheral T cell lymphoma (PTCL) is an aggressive form of non-Hodgkin's lymphoma characterized by a poor prognosis. In this study, we examined the prognostic value of two T-cell-specific transcription factors, GATA3 and T-bet, in PTCL, uncovered the pathogenesis of PTCL, and investigated new PTCL therapeutic targets. Samples from 109 PTCL patients were examined for expression of GATA3, T-bet and CD68. High GATA3 expression correlated with poor survival in PTCL patients and with tumor-associated macrophage (TAM) infiltration, as indicated by the presence of CD68-positive cells...
August 29, 2016: Oncotarget
Laura Maggi, Gianni Montaini, Alessio Mazzoni, Beatrice Rossettini, Manuela Capone, Maria Caterina Rossi, Veronica Santarlasci, Francesco Liotta, Oliviero Rossi, Oreste Gallo, Raffaele De Palma, Enrico Maggi, Lorenzo Cosmi, Sergio Romagnani, Francesco Annunziato
BACKGROUND: Protection against helminths consists of adaptive responses by TH2 cells and innate responses by group 2 innate lymphoid cells (ILC2s), with these latter being well characterized in mice but less so in human subjects. OBJECTIVE: We sought to characterize human circulating ILC2s and compare their functional profile with that of autologous TH2 cells. METHODS: Circulating ILC2s and TH2 cells were isolated by means of fluorescence-activated cell sorting and magnetic cell sorting and expanded in vitro...
July 27, 2016: Journal of Allergy and Clinical Immunology
E P Resende, A Todo-Bom, C Loureiro, A Mota Pinto, B Oliveiros, L Mesquita, H C Silva
BACKGROUND: Asthma and rhinitis have a complex etiology, depending on multiple genetic and environmental risk factors. An increasing number of susceptibility genes are currently being identified, but the majority of reported associations have not been consistently replicated across populations of different genetic backgrounds. PURPOSE: To evaluate whether polymorphisms of IL4R (rs1805015), IL13 (rs20541), IL17A (rs2275913) and GSTP1 (rs1695) genes are associated with rhinitis and/or asthma in adults of Portuguese ancestry...
August 22, 2016: Revista Portuguesa de Pneumologia
Katia Urso, David Alvarez, Viviana Cremasco, Kelly Tsang, Angelo Grauel, Robert Lafyatis, Ulrich H von Andrian, Joerg Ermann, Antonios O Aliprantis
Systemic sclerosis (SSc) is a potentially fatal autoimmune disorder with limited therapeutic options. Sclerodermatous graft versus host disease (sclGvHD), induced by transfer of B10.D2 splenocytes into BALB/c Rag2(-/-) mice, models an inflammatory subset of SSc characterized by a prominent IL13-induced gene expression signature in the skin. Host mice deficient in IL4RA, a subunit of the type II IL4/IL13 receptor, are protected from sclGvHD. While IL4RA has a well-established role in Th2 differentiation and alternative macrophage activation, we report here a previously unappreciated function for IL4RA in lymphatic endothelial cells (LECs): regulation of activated T cell egress...
August 4, 2016: JCI Insight
Peter C Smith, Caroline J Zeiss, Amanda P Beck, Jodi A Scholz
Demodex musculi, a prostigmatid mite that has been reported infrequently in laboratory mice, has been identified with increasing frequency in contemporary colonies of immunodeficient mice. Here we describe 2 episodes of D. musculi infestation with associated clinical signs in various genetically engineered mouse strains, as well as treatment strategies and an investigation into transmissibility and host susceptibility. The first case involved D. musculi associated with clinical signs and pathologic lesions in BALB/c-Tg(DO11...
2016: Comparative Medicine
Sun A Ock, Jungkyu Lee, Keon Bong Oh, Seongsoo Hwang, Ik Jin Yun, Curie Ahn, Hyun Keun Chee, Hwajung Kim, Jae Berm Park, Sung Joo Kim, Youngim Kim, Gi-Sun Im, EungWoo Park
Effective immunosuppression strategies and genetically modified animals have been used to prevent hyperacute and acute xenograft rejection; however, the underlying mechanisms remain unknown. In this study, we evaluated the expression of a comprehensive set of immune system-related genes (89 genes, including five housekeeping genes) in the blood of cynomolgus monkeys (~5 yr old) used as graft recipients, before and after the xenografting of the islets and heart from single and double α-1,3-galactosyltransferase (GalT) knockout (KO) pigs (<6 weeks old)...
September 2016: Xenotransplantation
Tian Bo Jin, Shuli Du, Xi Kai Zhu, Gang Li, Yongri Ouyang, Na He, Zhiying Zhang, Yuan Zhang, Longli Kang, Dongya Yuan
Inflammatory gene polymorphisms may be associated with glioma risk. The purpose of this study was to analyze effects of certain inflammatory gene and some clinical factors on patient survival.The clinical information of 269 glioma patients conceived operation from September 2010 to May 2014 to decide the 1-, 3-year survival rates according to follow-up results and analyze age, gender, the WHO classification, extent of surgical resection, radiotherapy and chemotherapy factors effects on prognosis. Survival distributions were estimated by using the Kaplan-Meier method and difference in the survival was tested using the log-rank test...
August 2016: Medicine (Baltimore)
Amir Hossein Massoud, Louis-Marie Charbonnier, David Lopez, Matteo Pellegrini, Wanda Phipatanakul, Talal A Chatila
Mechanisms by which regulatory T (Treg) cells fail to control inflammation in asthma remain poorly understood. We show that a severe asthma-associated polymorphism in the gene encoding the interleukin (IL)-4 receptor alpha chain (Il4ra(R576)) promotes conversion of induced Treg (iTreg) cells toward a T helper 17 (TH17) cell fate. This skewing is mediated by the recruitment by IL-4Rα(R576) of the growth-factor-receptor-bound protein 2 (GRB2) adaptor protein, which drives IL-17 expression by activating a pathway that involves extracellular-signal-regulated kinase, IL-6 and the transcription factor STAT3...
September 2016: Nature Medicine
T L Croston, A P Nayak, A R Lemons, W T Goldsmith, J K Gu, D R Germolec, D H Beezhold, B J Green
BACKGROUND: Personal exposure to fungal bioaerosols derived from contaminated building materials or agricultural commodities may induce or exacerbate a variety of adverse health effects. The genomic mechanisms that underlie pulmonary immune responses to fungal bioaerosols have remained unclear. OBJECTIVE: The impact of fungal viability on the pulmonary microRNA and messenger RNA profiles that regulate murine immune responses was evaluated following subchronic inhalation exposure to Aspergillus fumigatus conidia...
October 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
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