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David A Ewald, Shinji Noda, Margeaux Oliva, Thomas Litman, Saeko Nakajima, Xuan Li, Hui Xu, Peter Scheipers, Naila Svitacheva, Tord Labuda, James G Krueger, Mayte Suárez-Fariñas, Kenji Kabashima, Emma Guttman-Yassky
BACKGROUND: Atopic dermatitis (AD) is caused by a complex interplay between immune and barrier abnormalities. Murine models of AD are essential for preclinical assessments of new treatments. While many models have been used to simulate AD, their transcriptomic profiles are not fully understood, and a comparison of these models with the human AD transcriptomic fingerprint is lacking. OBJECTIVE: We sought to evaluate the transcriptomic profiles of six common murine models and determine how they relate to human AD skin...
October 1, 2016: Journal of Allergy and Clinical Immunology
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
Tianjing Liu, Yongyan Shi, Jie Du, Xin Ge, Xu Teng, Lu Liu, Enbo Wang, Qun Zhao
Crohn's disease (CD) and ulcerative colitis (UC) have different immunological mechanisms, while both of them are potential targets of vitamin D treatment. In this study, we have tried to address the role of vitamin D in CD and UC using two mouse models. Mice of C57B6L were given vitamin D before the induction of colitis. Our results showed that vitamin D attenuated 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis but not oxazolone-induced colitis. Vitamin D could preserve the local histology, alleviate inflammation, suppress apoptosis, maintain tight junction function and decrease permeability...
2016: Scientific Reports
Zhenlai Zhu, Yang Luo, Jinlei Yu, Jixin Gao, Yueqiang Zhang, Chunying Xiao, Chen Zhang, Gang Wang, Yufeng Liu, Meng Fu, Xu Yao, Wei Li
Originally recognized as a regulator of axon guidance in the nervous system, Semaphorin 4D (Sema4D, CD100) also participates in various immune responses and many immune-related diseases. However, whether Sema4D is involved in the pathogenesis of contact hypersensitivity (CHS) remains unclear. In this study, we explored the role of Sema4D in oxazolone-induced CHS using Sema4D knockout (KO) mice. We found that Sema4D KO mice developed attenuated CHS responses, as indicated by milder ear-swelling, lower expression of IL-1β, IL-6, CXCL2 and CXCL5, and decreased recruitment of neutrophils, CD8(+) T cells and CD4(+) T cells...
October 2016: Molecular Immunology
Wei Chen, Weixiong Chen, Jinshui Zhu, Niwei Chen, Yunmin Lu
The purpose of the current study was to evaluate the anti-inflammatory activity of tetramethlpyrazine on oxazolone-induced colitis mice. Spleen mononuclear cells (SMC), lamina propria mononuclear cells (LPMC) and peripheral blood mononuclear cells (PBMC) were isolated from oxazolone-induced colitis and normal mice. The colitis cells treated by oxazolone were randomly divided into model, low dose, middle dose and high dose groups treated with 0, 0.5, 1.0 and 2.0 g/L tetramethlpyrazine, respectively. The apoptotic rate of SMC and LPMC in the oxazolone-induced group was lower than that in the normal group...
2016: Iranian Journal of Pharmaceutical Research: IJPR
Safnas F AbdulSalam, Fathima Shazna Thowfeik, Edward J Merino
Although the terms "excessive reactive oxygen species (ROS)" and "oxidative stress" are widely used, the implications of oxidative stress are often misunderstood. ROS are not a single species but a variety of compounds, each with unique biochemical properties and abilities to react with biomolecules. ROS cause activation of growth signals through thiol oxidation and may lead to DNA damage at elevated levels. In this review, we first discuss a conceptual framework for the interplay of ROS and antioxidants. This review then describes ROS signaling using FLT3-mediated growth signaling as an example...
September 27, 2016: Biochemistry
Ryuichi Totsuka, Takaaki Kondo, Shigeki Matsubara, Midori Hirai, Yoichi Kurebayashi
VLA-1 (very late antigen-1) is implicated in recruitment, retention and activation of leukocytes and its blockade has been referred as a potential target of new drug discovery to address unmet medical needs in inflammatory disease area. In the present study, we investigate the effects of an anti-murine CD49a (integrin α subunit of VLA-1) monoclonal antibody (Ha31/8) on various experimental models of inflammatory diseases in mice. Pretreatment with Ha31/8 at an intraperitoneal dose of 250 µg significantly (P<0...
2016: Kobe Journal of Medical Sciences
Beata Jędrzejewska, Przemysław Krawczyk, Marek Józefowicz
Spectral and photophysical properties of two derivatives of the 2-phenyl-1,3-oxazol-5(4H)-ones were studied in 17 solvents of different polarity. These compounds have either push-pull non-centrosymmetric or C3-symmetric structures with electron-withdrawing groups (2-phenyl-oxazolone) introduced onto the triphenylamine. It has been found that their spectral and photophysical properties depend on the structure of the compounds and on the solvent polarity. The non-radiative relaxation process is facilitated by an increase of the solvent polarity...
January 15, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Ziwei Liu, Lukas Rigger, Jean-Christophe Rossi, John D Sutherland, Robert Pascal
5(4H)-Oxazolones can be formed through the activation of acylated α-amino acids or of peptide C termini. They constitute potentially activated intermediates in the abiotic chemistry of peptides that preceded the origin of life or early stages of biology and are capable of yielding mixed carboxylic-phosphoric anhydrides upon reaction with phosphate esters and nucleotides. Here, we present the results of a study aimed at investigating the chemistry that can be built through this interaction. As a matter of fact, the formation of mixed anhydrides with mononucleotides and nucleic acid models is shown to take place at positions involving a mono-substituted phosphate group at the 3'- or 5'-terminus but not at the internal phosphodiester linkages...
October 10, 2016: Chemistry: a European Journal
Tina Rubić-Schneider, Nicole Carballido-Perrig, Camille Regairaz, Layla Raad, Sandra Jost, Celine Rauld, Brigitte Christen, Grazyna Wieczorek, Robert Kreutzer, Janet Dawson, Günther Lametschwandner, Amanda Littlewood-Evans, José M Carballido
BACKGROUND: Succinate, in addition to its role as an intermediary of the citric acid cycle, acts as an alarmin, initiating and propagating danger signals resulting from tissue injury or inflammatory stimuli. The contribution of this immune sensing pathway to the development of allergic and inflammatory responses is unknown. METHODS: Ear thickness of wild type (wt) and Sucnr1 deficient (Sucnr1 (-/-) ) mice, sensitized and challenged with oxazolone, was used as a criterion to assess the relevance of SUCNR1/GPR91 expression mediating allergic contact dermatitis (ACD)...
August 16, 2016: Allergy
Pia Palamides, Henrika Jodeleit, Michael Föhlinger, Florian Beigel, Nadja Herbach, Thomas Mueller, Eckhard Wolf, Matthias Siebeck, Roswitha Gropp
Animal models reflective of ulcerative colitis (UC) remain a major challenge, and yet are crucial to understand mechanisms underlying the onset of disease and inflammatory characteristics of relapses and remission. Mouse models in which colitis-like symptoms are induced through challenge with toxins such as oxazolone, dextran sodium sulfate (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS) have been instrumental in understanding the inflammatory processes of UC. However, these neither reflect the heterogeneous symptoms observed in the UC-affected population nor can they be used to test the efficacy of inhibitors developed against human targets where high sequence and structural similarity of the respective ligands is lacking...
September 1, 2016: Disease Models & Mechanisms
Pei Li, Yuming Zhao, Lihong Ge
BACKGROUND: The immunomodulatory and anti-inflammatory functions of human gingiva-derived mesenchymal stromal cells (GMSCs) have been demonstrated in contact hypersensitivity (CHS) models; however, their therapeutic effect during the late phase of CHS has been poor. METHODS: The murine CHS model was induced by applying oxazolone to the ears of mice. Mesenchymal stromal cells were applied via two methods (intravenous or local injection) at three time points: 1 day before sensitization, 1 day before challenge, or 1 h after challenge...
2016: Stem Cell Research & Therapy
Muhammad Akram, Iljin Shin, Kyeong-A Kim, Dabi Noh, Seung-Hoon Baek, Sun-Young Chang, Hyoungsu Kim, Ok-Nam Bae
Impaired immune responses in skin play a pivotal role in the development and progression of chemical-associated inflammatory skin disorders. In this study, we synthesized new flavonoid derivatives from macakurzin C, and identified in vitro and in vivo efficacy of a potent anti-inflammatory flavonoid, Compound 14 (CPD 14), with its underlying mechanisms. In lipopolysaccharide (LPS)-stimulated murine macrophages and IFN-γ/TNF-α-stimulated human keratinocytes, CPD 14 significantly inhibited the release of inflammatory mediators including nitric oxide (NO), prostaglandins, and cytokines (IC50 for NO inhibition in macrophages: 4...
September 15, 2016: Toxicology and Applied Pharmacology
Alexander A Chumanevich, Erin E Witalison, Anusha Chaparala, Anastasiya Chumanevich, Prakash Nagarkatti, Mitzi Nagarkatti, Lorne J Hofseth
BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is associated with an increased risk of colorectal cancer in 8-10 years after disease onset. Current colitis treatment strategies do not offer a cure for the disease, but only treat the symptoms with limited success and dangerous side-effects. Also, there is no preventive treatment for either UC or colorectal cancer. Quinacrine is an anti-malarial drug with versatile use in the treatment of diseases involving inflammatory response such as rheumatoid arthritis and lupus erythematosus...
July 14, 2016: Oncotarget
Yi Yao, Yun Liu, Akira Takashima
Neutrophils are the most abundant leukocytes in human blood circulation and are quickly recruited to inflammatory sites. Priming is a critical event that enhances the phagocytic functionality of neutrophils. Although extensive studies have unveiled the existence and importance of neutrophil priming during infection and injury, means of visualizing this process in vivo have been unavailable. The protocol provided enables monitoring of the dynamic process of neutrophil priming in living animals by combining three methodologies: 1) DsRed reporter signal - used as a measure of priming 2) in vivo neutrophil labeling - achieved by injection of fluorescence-conjugated anti-lymphocyte antigen 6G (Ly6G) monoclonal antibody (mAb) and 3) intravital confocal imaging...
2016: Journal of Visualized Experiments: JoVE
Simone Gräßle, Sylvia Vanderheiden, Patrick Hodapp, Bekir Bulat, Martin Nieger, Nicole Jung, Stefan Bräse
A solid supported procedure for the synthesis of benzoxazinones, dihydropyrazinones, quinoxalinones, and dihydrooxazinones using immobilized oxazolones in combination with difunctional nucleophiles as cleavage agent is presented. The scope of the novel method has been demonstrated through subsequent modification of the parent oxazolone scaffold on solid supports using conversions with electrophiles or CuAAC reactions to give functionalized pyrazin-2-ones. The described method allows the synthesis of the target heterocycles in good yields via three to five steps on solid phases with only one chromatographic purification step...
August 5, 2016: Organic Letters
Marcin Mączyński, Jolanta Artym, Maja Kocięba, Iwona Kochanowska, Stanisław Ryng, Michał Zimecki
BACKGROUND: A series of new isoxazole derivatives of expected immunosuppressive activities was synthesized. Following in vitro screening in the human cell models, the activity of MZO-2 compound (ethyl N-{4-[(2,4-dimethoxybenzyl)carbamoyl]-3-methylisoxazol-5-yl}acetimidate) in mouse in vivo models was evaluated. METHODS: In vitro tests included evaluation of: peripheral blood mononuclear cells (PBMC) viability, phytohemagglutinin (PHA)-induced PBMC proliferation and lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNF α) production in whole blood cell cultures...
October 2016: Pharmacological Reports: PR
Justin Kai-Chi Lau, Junfang Zhao, Declan Williams, Bai-Han Backen Wu, Yating Wang, Stefanie Mädler, Irine S Saminathan, K W Michael Siu, Alan C Hopkinson
Macrocyclization is commonly observed in large bn(+) (n≥ 4) ions and as a consequence can lead to incorrect protein identification due to sequence scrambling. In this work, the analogous [b5- H]˙(+) radical cations derived from aliphatic hexapeptides (GA5˙(+)) also showed evidence of macrocyclization under CID conditions. However, the major fragmentation for [b5- H]˙(+) ions is the loss of CO2 and not CO loss, which is commonly observed in closed-shell bn(+) ions. Isotopic labeling using CD3 and (18)O revealed that more than one common structure underwent dissociations...
July 21, 2016: Physical Chemistry Chemical Physics: PCCP
Su-Min Lim, Sang-Yun Lee, Jin-Ju Jeong, Hyun Sik Choi, Hwan Bong Chang, Dong-Hyun Kim
In the previous study, the rhizome mixture of Anemarrhena asphodeloides and Coptis chinensis (DW2007), improved TNBS-, oxazolone-, or DSS-induced colitis in mice by regulating macrophage activation. Therefore, to understand the effect of DW2007 on the T cell differentiation involved in the adaptive immunity, we measured its effect on both Th17 and Treg cell differentiation in splenocytes, in the lamina propria of mice with DSS-induced colitis (DIC), and in the spleens of mice with collagen-induced arthritis (CIA)...
June 17, 2016: Biomolecules & Therapeutics
Xuewei Wang, Fugang Fan, Qin Cao
Inflammatory bowel diseases (IBDs) are chronic inflammatory gastrointestinal disorders caused by a dysregulated mucosal immune response and epithelial barrier disruption. Conventional treatment of IBD is currently limited to overcoming patient symptoms and is often associated with severe adverse effects from the drugs used. Modified Pulsatilla decoction has been used previously to treat ulcerative colitis (UC) in clinical practice in China, however, the underlying mechanism in the treatment of UC remains to be elucidated...
August 2016: Molecular Medicine Reports
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