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Marco Pio La Manna, Valentina Orlando, Paolo Li Donni, Guido Sireci, Paola Di Carlo, Antonio Cascio, Francesco Dieli, Nadia Caccamo
We used the Luminex Bead Array Multiplex Immunoassay to measure cytokines, chemokines and growth factors responses to the same antigens used for RD1-based Interferon γ Release Assay (IGRA) test. Seventy-nine individuals, 27 active TB, 32 latent infection subsets, 20 individuals derivative purified protein (PPD) negative (subjects that do not have any indurative cutaneous reaction after 72 hrs of intradermal injection of PPD) and with other pulmonary disease were retrospectively studied. Forty-eight analytes were evaluated by Luminex Assay in plasma obtained from whole blood stimulated cells...
2018: PloS One
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
Antonio Rodriguez-Nicolas, Alba Martínez-Chamorro, Pilar Jiménez, Ana M Matas-Cobos, Eduardo Redondo-Cerezo, Francisco Ruiz-Cabello
OBJECTIVES: Acute pancreatitis (AP) is severe in up to 20% of patients, with a high mortality rate. Quantification of serum TH1 and TH2 cytokines may provide objective evidence to assess the severity of AP and predict its course. METHODS: One hundred seventeen patients were studied, measuring serum concentrations of interleukin (IL)1β, IL2, IL4, IL5, IL6, IL10, IL12p70, IL13, IL18, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN) γ, and tumor necrosis factor (TNF) α...
April 2018: Pancreas
Erin E Olsan, Jonathan D West, Jacob A Torres, Nicholas Doerr, Thomas Weimbs
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a life-threatening, highly prevalent monogenic disease caused by mutations in polycystin-1 (PC1) in 85% of patients. We have previously identified a C-terminal cleavage fragment of PC1, PC1-p30, that interacts with the transcription factor STAT6 to promote transcription. STAT6 is aberrantly active in PKD mouse models and human ADPKD, and genetic removal or pharmacological inhibition of STAT6 attenuates disease progression. High levels of interleukin-13 (IL13), a STAT6 activating cytokine, are found in the cyst fluid of PKD mouse models and increased IL13 receptors in ADPKD patient tissue suggesting that a positive feedback loop between IL13 and STAT6 is activated in cystic epithelial cells and contributes to disease progression...
March 7, 2018: American Journal of Physiology. Renal Physiology
Omar M Rahal, Adam R Wolfe, Pijus K Mandal, Richard Larson, Sanda Tin, Cristina Jimenez, Dadong Zhang, Janet Horton, James M Reuben, John S McMurray, Wendy A Woodward
PURPOSE: To determine the role of macrophage polarization on the response of inflammatory breast cancer (IBC) cells to radiation and whether modulation of macrophage plasticity can alter radiation response. METHODS AND MATERIALS: The human THP-1 monocyte cell line and primary human monocytes isolated from peripheral blood mononuclear cells were differentiated into macrophages and polarized to either an "antitumor" (M1) or a "protumor" (M2) phenotype...
March 15, 2018: International Journal of Radiation Oncology, Biology, Physics
Raffaela Zaffini, Giovanni Gotte, Marta Menegazzi
Asthma is a chronic lung disease affecting people of all ages worldwide, and it frequently begins in childhood. Because of its chronic nature, it is characterized by pathological manifestations, including airway inflammation, remodeling, and goblet cell hyperplasia. Current therapies for asthma, including corticosteroids and beta-2 adrenergic agonists, are directed toward relieving the symptoms of the asthmatic response, with poor effectiveness against the underlying causes of the disease. Asthma initiation and progression depends on the T helper (Th) 2 type immune response carried out by a complex interplay of cytokines, such as interleukin (IL) 4, IL5, and IL13, and the signal transducer and activator of transcription 6...
2018: Drug Design, Development and Therapy
Sofia P Rebelo, Catarina Pinto, Tatiana R Martins, Nathalie Harrer, Marta F Estrada, Pablo Loza-Alvarez, José Cabeçadas, Paula M Alves, Emilio J Gualda, Wolfgang Sommergruber, Catarina Brito
The tumour microenvironment (TME) shapes disease progression and influences therapeutic response. Most aggressive solid tumours have high levels of myeloid cell infiltration, namely tumour associated macrophages (TAM). Recapitulation of the interaction between the different cellular players of the TME, along with the extracellular matrix (ECM), is critical for understanding the mechanisms underlying disease progression. This particularly holds true for prediction of therapeutic response(s) to standard therapies and interrogation of efficacy of TME-targeting agents...
May 2018: Biomaterials
Cunxue Zhang, Peili Yang, Yan Chen, Jing Liu, Xiutai Yuan
The aim of the present study was to detect DACT1 expression levels in the lungs of children with asthma, and to investigate its role and molecular mechanisms in regulating the expression of inflammatory factors in RAW264.7 cells. DACT1, DACT2 and DACT3 expression was analyzed in biopsy specimens from 10 cases of newly diagnosed children with asthma and 10 healthy controls by reverse transcription-quantitative polymerase chain reaction, and their expression was confirmed in RAW264.7 cells. DACT1 expression was silenced by small interfering RNA or enhanced by transfection of pcDNA-3...
March 2018: Experimental and Therapeutic Medicine
Hui Fang Lim, Parameswaran Nair
Severe asthma is a complex disease consisting of different endotypes with different inflammatory and clinicopathological characteristics due to the heterogeneity of immune responses and smooth muscle dysfunction. There is an unmet clinical need to develop and to validate biomarkers that can differentiate between the asthma endotypes and guide clinical management, particularly since the availability of biologicals directed against T2 cytokines. The presence of a "Th2 endotype" is currently assessed in clinical practice using markers, such as eosinophil count in sputum or blood, fraction of exhaled nitric oxide, and immunoglobulin E...
February 2018: Seminars in Respiratory and Critical Care Medicine
Indhupriya Subramanian, Vivek K Singh, Abhay Jere
BACKGROUND: Topical Betamethasone (BM) and Pimecrolimus (PC) are widely used drugs in the treatment of atopic dermatitis (AD). Though the biomolecules and biological pathways affected by the drugs are known, the causal inter-relationships among these pathways in the context of skin is not available. We aim to derive this insight by using transcriptomic data of AD skin samples treated with BM and PC using systems biology approach. METHODS: Transcriptomic datasets of 10 AD patients treated with Betamethasone and Pimecrolimus were obtained from GEO datasets...
February 7, 2018: BMC Dermatology
David Chiang, Xintong Chen, Stacie M Jones, Robert A Wood, Scott H Sicherer, A Wesley Burks, Donald Y M Leung, Charuta Agashe, Alexander Grishin, Peter Dawson, Wendy F Davidson, Leah Newman, Robert Sebra, Miriam Merad, Hugh A Sampson, Bojan Losic, M Cecilia Berin
BACKGROUND: The contribution of phenotypic variation of peanut-specific T cells to clinical allergy or tolerance to peanut is not well understood. OBJECTIVES: Our objective was to comprehensively phenotype peanut-specific T cells in the peripheral blood of individuals with and without peanut allergy (PA). METHODS: We obtained samples from PA individuals, including a cohort undergoing baseline peanut challenges for an immunotherapy trial (CoFAR6)...
January 30, 2018: Journal of Allergy and Clinical Immunology
Yong-Dong Lin, Xing-Liang Fan, Hong Zhang, Shu-Bin Fang, Cheng-Lin Li, Meng-Xia Deng, Zi-Li Qin, Ya-Qi Peng, Hong-Yu Zhang, Qing-Ling Fu
BACKGROUND: Asthma is affecting more than 300 million people worldwide, which represents the most common chronic disease among children. We previously found that mesenchymal stem cells (MSCs) derived from induced pluripotent stem cells (iPSCs) modulated the immune response on Th2-mediated asthma in vivo and in vitro. This study further evaluated the immunomodulatory effects of MSCs from human embryonic stem cells (hESCs) on asthma. METHODS: Multipotent hESC-MSCs were obtained using a feeder-free method...
January 31, 2018: Molecular Immunology
Donald P Tashkin, Michael E Wechsler
COPD is a significant cause of morbidity and mortality. In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation. Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy. In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention...
2018: International Journal of Chronic Obstructive Pulmonary Disease
Giuseppina Campisciano, Nunzia Zanotta, Danilo Licastro, Francesco De Seta, Manola Comar
The microbiota fulfils a key role in the training and function of the immune system, which contributes to the symbiosis between the host and complex microbial communities. In this study, we characterized the interplay between vaginal bacteria and local immune mediators during dysbiosis in selected women of reproductive age who were grouped according to Nugent's criteria. The abundance of Gardnerella vaginalis and Bifidobacterium breve was increased in the intermediate dysbiotic status, while the presence of a plethora of non-resident bacteria characterized the group with overt vaginosis...
February 2, 2018: Scientific Reports
Quanhui Mei, Jingjing Qu
A number of studies have reported that the interleukin 13 (IL-13) gene is associated with asthma susceptibility. However, the reported relationships between the +2044G/A and +1923C/T polymorphisms and asthma susceptibility are inconsistent, especially in Asian adults and children with atopic status. Meta-analysis was used to analyze combined data.The +2044G/A and +1923C/T polymorphisms were investigated using data from 18 and 11 studies, respectively. The results suggested that there was an association between asthma and the IL-13 +2044G/A polymorphisms: odds ratio (OR) 1...
December 2017: Medicine (Baltimore)
N Y Yoon, H Y Wang, M Jun, M Jung, D H Kim, N R Lee, K-W Hong, S J Seo, E Choi, J Lee, H Lee, E H Choi
BACKGROUND: Hereditary factors are involved in the pathogenesis of atopic dermatitis (AD). However, AD-related gene variations are significantly different across ethnicities. AIM: To identify mutations and single-nucleotide polymorphisms (SNPs) in barrier- or immune-related genes from Korean patients with AD and compare the variations with those observed in nonatopic healthy controls (HCs), and to use novel reverse blot hybridization assay (REBA) for AD-related gene variants...
January 30, 2018: Clinical and Experimental Dermatology
Bahadır Batar, Sezen Özman, Kenan Barut, Özgür Kasapçopur, Mehmet Güven
Background/aim: Juvenile idiopathic arthritis (JIA) is a chronic complex autoimmune disease. Genetic and environmental factors increase the risk of JIA. It is accepted that alterations in immune system pathways play an important role in the pathogenesis of JIA. The aim of the study was to investigate the possible association between immune system regulatory gene polymorphisms and JIA in Turkish patients. Materials and methods: We analyzed eight polymorphisms, TNF-alpha-863 C > A, TNFRII 196 T > G, IL2-631 G > A, IL13-1112 C > T, CCR2 190 G > A, CCR5delta32, CTLA4-1661 A > G, and PTPN22 1858 C > T, in 76 patients with JIA and in 80 healthy controls, who were of a similar age and same sex...
December 19, 2017: Turkish Journal of Medical Sciences
A B Madhankumar, Oliver D Mrowczynski, Becky Slagle-Webb, Vagisha Ravi, Alexandre J Bourcier, Russell Payne, Kimberly S Harbaugh, Elias Rizk, James R Connor
Peripheral nerve sheath tumors are benign tumors that have the potential to transform into malignant peripheral nerve sheath tumors (MPNSTs). Interleukin-13 receptor alpha 2 (IL13Rα2) is a cancer associated receptor expressed in glioblastoma and other invasive cancers. We analyzed IL13Rα2 expression in several MPNST cell lines including the STS26T cell line, as well as in several peripheral nerve sheath tumors to utilize the IL13Rα2 receptor as a target for therapy. In our studies, we demonstrated the selective expression of IL13Rα2 in several peripheral nerve sheath tumors by immunohistochemistry (IHC) and immunoblots...
2018: PloS One
Koustav Sarkar, Seong-Su Han, Kuo-Kwang Wen, Hans D Ochs, Loïc Dupré, Michael M Seidman, Yatin M Vyas
BACKGROUND: Wiskott-Aldrich syndrome (WAS), X-linked thrombocytopenia (XLT), and X-linked neutropenia (XLN), caused by WAS mutations affecting WASp expression or activity, manifest in immunodeficiency, autoimmunity, genomic-instability, and lymphoid-cancer. WASp supports filamentous-actin formation in the cytoplasm and gene-transcription in the nucleus. Although the genetic basis for XLT/WAS has been clarified, the relationships between mutant forms of WASp and the diverse features of these disorders remain ill-defined...
December 14, 2017: Journal of Allergy and Clinical Immunology
Hans O Kalkman, Dominik Feuerbach
Atopic diseases are frequently co-morbid with autism spectrum disorders (ASD). Allergic responses are associated with an activation of mast cells, innate lymphoid cells, and Th2 cells. These cells produce type-2 cytokines (IL4 and IL13), which stimulate microglia and macrophages to adopt a phenotype referred to as 'alternative activation' or 'M2A'. M2A-polarized macrophages and microglia play a physiological role in tissue repair by secreting growth factors such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1...
December 9, 2017: Pharmaceuticals
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