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https://www.readbyqxmd.com/read/29049008/exogenous-murine-antimicrobial-peptide-cramp-significantly-exacerbates-ovalbumin-induced-airway-inflammation-but-ameliorates-oxazolone-induced-intestinal-colitis-in-balb-c-mice
#1
Yang Li, Xiaojie Chu, Cunbao Liu, Weiwei Huang, Yufeng Yao, Ye Xia, Pengyan Sun, Qiong Long, Xuejun Feng, Kui Li, Xu Yang, Hongmei Bai, Wenjia Sun, Yanbing Ma
Cathelicidin has been reported to be multifunctional. The current study aimed to investigate the influences of exogenous cathelicidin-related antimicrobial peptide (CRAMP) on inflammatory responses in different disease models. In OVA-induced allergic airway inflammation, CRAMP significantly enhanced the infiltration of inflammatory cells and accumulation of proinflammatory Th2 cytokine IL-13 and IL-33 in bronchial alveolar lavage fluid (BALF), exacerbated lung tissue inflammation and airway goblet cell hyperplasia, and elevated OVA-specific IgE level in serum...
October 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29043360/synthesis-photophysical-and-biological-properties-of-a-new-oxazolone-fluorescent-probe-for-bioimaging-an-experimental-and-theoretical-study
#2
Przemysław Krawczyk, Beata Jędrzejewska, Piotr Cysewski, Tomasz Janek
In this study, a new oxazolone derivative 4-{N,N-bis[2-phenyl-4-benzylidene-1,3-oxazol-5(4H)-one]amino}benzaldehyde (PB3) was synthesized and investigated as a fluorescent dye. The spectroscopic properties in different solvents were thoroughly studied. The experimental data were supported by quantum-chemical calculations using density functional theory. Measurements and theoretical calculations showed that the PB3 dye is characterized by non-monotonic solvatochromism, a strongly polar charge transfer excited state, a large Stokes' shift, a high fluorescence quantum yield and a high fluorescence lifetime...
October 18, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28962179/evaluation-of-hyaluronic-acid-p40-conjugated-cream-in-a-mouse-model-of-dermatitis-induced-by-oxazolone
#3
Katia Mangano, Franca Vergalito, Santa Mammana, Andrea Mariano, Rocco De Pasquale, Antonia Meloscia, Silvia Bartollino, Germano Guerra, Ferdinando Nicoletti, Roberto Di Marco
P40 is a particulate fraction or fragment isolated from Corynebacterium granulosum, which exhibits a wide spectrum of pharmacological functions including antitumor, antibacterial, phagocytic, antiviral and cytokine induction effects. In the present study, the immunomodulatory potential of P40-conjugated with hyaluronic acid was assessed in a mouse model of dermatitis induced by oxazolone. Oxazolone-induced allergic contact dermatitis is a T cell-mediated Th2-like hypersensitivity reaction, which mimics the corresponding reaction in humans...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28957753/structure-based-design-of-herg-neutral-antihypertensive-oxazalone-and-imidazolone-derivatives
#4
Busecan Aksoydan, Isik Kantarcioglu, Ismail Erol, Ramin Ekhteiari Salmas, Serdar Durdagi
Angiotensin II receptor type 1 (AT1) antagonists are the most recent drug class against hypertension. Recently first crystal structure of AT1 receptor is deposited to the protein data bank (PDB ID: 4YAY). In this work, several molecular screening methods such as molecular docking and de novo design studies were performed and it is found that oxazolone and imidazolone derivatives reveal similar/better interaction energy profiles compared to the FDA approved sartan molecules at the binding site of the AT1 receptor...
August 12, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28912045/sulfate-reducing-bacteria-stimulate-gut-immune-responses-and-contribute-to-inflammation-in-experimental-colitis
#5
Vanessa Ribeiro Figliuolo, Liliane Martins Dos Santos, Alessandra Abalo, Hayandra Nanini, Angela Santos, Nilda M Brittes, Claudio Bernardazzi, Heitor Siffert Pereira de Souza, Leda Quercia Vieira, Robson Coutinho-Silva, Claudia Mara Lara Melo Coutinho
The intestinal microbiota is critical for mammalian immune system development and homeostasis. Sulfate-reducing bacteria (SRB) are part of the normal gut microbiota, but their increased levels may contribute to colitis development, likely in association with hydrogen sulfide (H2S) production. Here, we investigated the effects of SRB in the gut immune response in germ-free mice, and in experimental colitis. After 7days of colonization with Desulfovibrio indonesiensis or with a human SRB consortium (from patients with colitis), germ-free mice exhibited alterations in the colonic architecture, with increased cell infiltration in the lamina propria...
September 11, 2017: Life Sciences
https://www.readbyqxmd.com/read/28892206/il-33-and-ige-stimulate-mast-cell-production-of-il-2-and-regulatory-t-cells-expansion-in-allergic-dermatitis
#6
Pazit Salamon, Irit Shefler, Itay Moshkovits, Ariel Munitz, Deborah Horwitz Klotzman, Yoseph A Mekori, Alon Y Hershko
BACKGROUND: We have previously shown that mast cells (MCs) suppress chronic allergic dermatitis in mice. The underlying mechanism involves MC-derived IL-2, which supports regulatory T cell (Treg) response at the site of inflammation. However, it is not clear what are the factors that drive MCs to produce IL-2. OBJECTIVE: To understand the mechanisms that lead to IL-2 production from MCs in chronic allergic dermatitis. METHODS: Isolated murine bone marrow derived-MCs (BMMCs) were incubated with various stimulators and IL-2 production was assessed by RT-PCR and ELISA...
September 11, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28862441/reaction-of-ynamides-with-iminoiodinane-derived-nitrenes-formation-of-oxazolones-and-polyfunctionalized-oxazolidinones
#7
Romain Rey-Rodriguez, Gwendal Grelier, Loïc Habert, Pascal Retailleau, Benjamin Darses, Isabelle Gillaizeau, Philippe Dauban
This article describes the reaction of ynamides with metallanitrenes generated in the presence of an iodine(III) oxidant. N-(Boc)-Ynamides are converted to oxazolones via a cyclization reaction. The reaction is mediated by a catalytic dirhodium-bound nitrene species that first behaves as a Lewis acid. The oxazolones can be converted in a one pot manner to functionalized oxazolidinones following a regio- and stereoselective oxyamination reaction with the same nitrene reagent generated in stoichiometric amounts...
September 1, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28842393/e6130-a-novel-cx3c-chemokine-receptor-1-cx3cr1-modulator-attenuates-mucosal-inflammation-and-reduces-cx3cr1-leukocyte-trafficking-in-mice-with-colitis
#8
Hisashi Wakita, Tatsuya Yanagawa, Yoshikazu Kuboi, Toshio Imai
The chemokine fractalkine (CX3C chemokine ligand 1; CX3CL1) and its receptor CX3CR1 are involved in the pathogenesis of several diseases, including inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, rheumatoid arthritis, hepatitis, myositis, multiple sclerosis, renal ischemia, and atherosclerosis. There are no orally available agents that modulate the fractalkine/CX3CR1 axis. [(3S,4R)-1-[2-Chloro-6-(trifluoromethyl)benzyl]-3-{[1-(cyclohex-1-en-1-ylmethyl)piperidin-4-yl]carbamoyl}-4-methylpyrrolidin-3-yl]acetic acid (2S)-hydroxy(phenyl)acetate (E6130) is an orally available highly selective modulator of CX3CR1 that may be effective for treatment of inflammatory bowel disease...
November 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28826779/gene-expression-profiles-in-auricle-skin-as-a-possible-additional-endpoint-for-determination-of-sensitizers-a-multi-endpoint-evaluation-of-the-local-lymph-node-assay
#9
Hiromi Tsuchiyama, Akihisa Maeda, Mayumi Nakajima, Mika Kitsukawa, Kei Takahashi, Tomoya Miyoshi, Mayu Mutsuga, Yoshiji Asaoka, Yohei Miyamoto, Keiyu Oshida
The murine local lymph node assay (LLNA) is widely used to test chemicals to induce skin sensitization. Exposure of mouse auricle skin to a sensitizer results in proliferation of local lymph node T cells, which has been measured by in vivo incorporation of H(3)-methyl thymidine or 5-bromo-2'-deoxyuridine (BrdU). The stimulation index (SI), the ratio of the mean proliferation in each treated group to that in the concurrent vehicle control group, is frequently used as a regulatory-authorized endpoint for LLNA...
October 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28818461/discovery-and-process-development-of-a-novel-tace-inhibitor-for-the-topical-treatment-of-psoriasis
#10
Jean-Guy Boiteau, Gilles Ouvry, Jean-Marie Arlabosse, Stéphanie Astri, Audrey Beillard, Yushma Bhurruth-Alcor, Laetitia Bonnary, Claire Bouix-Peter, Karine Bouquet, Marilyne Bourotte, Isabelle Cardinaud, Catherine Comino, Benoît Deprez, Denis Duvert, Angélique Féret, Feriel Hacini-Rachinel, Craig S Harris, Anne-Pascale Luzy, Arnaud Mathieu, Corinne Millois, Nicolas Orsini, Jonathan Pascau, Artur Pinto, David Piwnica, Gaëlle Polge, Arnaud Reitz, Kevin Reversé, Nicolas Rodeville, Patricia Rossio, Delphine Spiesse, Samuel Tabet, Nathalie Taquet, Loïc Tomas, Emmanuel Vial, Laurent F Hennequin
Targeting the TNFα pathway is a validated approach to the treatment of psoriasis. In this pathway, TACE stands out as a druggable target and has been the focus of in-house research programs. In this article, we present the discovery of clinical candidate 26a. Starting from hits plagued with poor solubility or genotoxicity, 26a was identified through thorough multiparameter optimisation. Showing robust in vivo activity in an oxazolone-mediated inflammation model, the compound was selected for development. Following a polymorph screen, the hydrochloride salt was selected and the synthesis was efficiently developed to yield the API in 47% overall yield...
August 2, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28807557/the-role-of-toll-like-receptor-3-in-chronic-contact-hypersensitivity-induced-by-repeated-elicitation
#11
Risa Yasuike, Risa Tamagawa-Mineoka, Mayumi Ueta, Naomi Nakamura, Shigeru Kinoshita, Norito Katoh
BACKGROUND: Accumulating evidence suggests that Toll-like receptor (TLR)-3 signaling is involved in non-infectious immune and inflammatory reactions as well as in viral infections. The skin of patients with atopic dermatitis (AD) is often infected with virus and bacteria, leading to the aggravation of atopic symptoms. These findings suggest TLR3 signaling may be involved in the pathogenesis of AD, but the exact role of TLR3 in AD remains to be defined. OBJECTIVE: The purpose of this study was to investigate the role of TLR3 in chronic contact hypersensitivity reactions induced by repeated elicitation, resembling the features of AD...
August 4, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28781714/generation-repair-and-replication-of-guanine-oxidation-products
#12
REVIEW
Katsuhito Kino, Masayo Hirao-Suzuki, Masayuki Morikawa, Akane Sakaga, Hiroshi Miyazawa
Guanine is the most readily oxidized of the four DNA bases, and guanine oxidation products cause G:C-T:A and G:C-C:G transversions through DNA replication. 8-Oxo-7,8-dihydroguanine (8-oxoG) causes G:C-T:A transversions but not G:C-C:G transversions, and is more readily oxidized than guanine. This review covers four major findings. (i) 2,2,4-Triamino-5(2H)-oxazolone (Oz) is produced from guanine and 8-oxoG under various oxidative conditions. Guanine is incorporated opposite Oz by DNA polymerases, except REV1...
2017: Genes and Environment: the Official Journal of the Japanese Environmental Mutagen Society
https://www.readbyqxmd.com/read/28748525/topically-applied-azaphenothiazines-inhibit-contact-sensitivity-to-oxazolone-in-mice
#13
Jolanta Artym, Maja Kocięba, Ewa Zaczyńska, Michał Zimecki, Małgorzata Jeleń, Beata Morak-Młodawska, Krystian Pluta, Katarzyna Kaleta-Kuratewicz, Jan P Madej, Piotr Kuropka, Jan Kuryszko
In this work we investigated the efficacy of two topically applied azaphenothiazine derivatives, 9-chloro-6-acetylaminobutylquinobenzo[3,2-b][1,4]thiazine (compound 4) and 6-chloroethylureidoethyldiquino[3,2-b;2';3'-e][1,4]thiazine (compound 5), in the amelioration of inflammatory symptoms of contact sensitivity (CS) to oxazolone in mice, in relation to the commercial ointment Protopic® (tacrolimus), the reference drug. The compounds were administered 24 h following elicitation of CS and, 24 h later, the parameters of inflammation, such as ear edema, blood composition, leukocyte level, numbers of cells in the draining lymph nodes, histological picture of the inflamed tissue, and the morphometric analysis, were analyzed...
July 27, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28667471/topical-application-of-dermatophagoides-farinae-or-oxazolone-induces-symptoms-of-atopic-dermatitis-in-the-rabbit-ear
#14
Jingling Zhao, Shengxian Jia, Ping Xie, Gabriel A Arenas, Robert D Galiano, Seok Jong Hong, Thomas A Mustoe
Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease characterized by hyperproliferation and abnormal differentiation of the epidermis, and dermal infiltration of inflammatory cells. Appropriate animal models that recapitulate human AD and allow the analysis of disease processes in a reliable manner are essential to the study of AD. In this study, we established two AD models in rabbits by applying an allergen, Dermatophagoides farinae (Der f), or a hapten, oxazolone (OXZ). Application of the allergen or hapten induced a rapid onset and a chronically sustained AD-like skin lesion...
June 30, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28607110/the-bile-acid-receptor-gpbar1-regulates-the-m1-m2-phenotype-of-intestinal-macrophages-and-activation-of-gpbar1-rescues-mice-from-murine-colitis
#15
Michele Biagioli, Adriana Carino, Sabrina Cipriani, Daniela Francisci, Silvia Marchianò, Paolo Scarpelli, Daniele Sorcini, Angela Zampella, Stefano Fiorucci
GPBAR1 (TGR5 or M-BAR) is a G protein-coupled receptor for secondary bile acids that is highly expressed in monocytes/macrophages. In this study, we aimed to determine the role of GPBAR1 in mediating leukocyte trafficking in chemically induced models of colitis and investigate the therapeutic potential of BAR501, a small molecule agonist for GPBAR1. These studies demonstrated that GPBAR1 gene ablation enhanced the recruitment of classically activated macrophages in the colonic lamina propria and worsened the severity of inflammation...
July 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28583370/prostaglandin-e2-stimulates-adaptive-il-22-production-and-promotes-allergic-contact-dermatitis
#16
Calum T Robb, Henry J McSorley, Jinju Lee, Tomohiro Aoki, Cunjing Yu, Siobhan Crittenden, Anne Astier, Jennifer M Felton, Nicholas Parkinson, Adane Ayele, Richard M Breyer, Stephen M Anderton, Shuh Narumiya, Adriano G Rossi, Sarah E Howie, Emma Guttman-Yassky, Richard B Weller, Chengcan Yao
BACKGROUND: Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are both forms of eczema and are common inflammatory skin diseases with a central role of T cell-derived IL-22 in their pathogenesis. Although prostaglandin (PG) E2 is known to promote inflammation, little is known about its role in processes related to AD and ACD development, including IL-22 upregulation. OBJECTIVES: We sought to investigate whether PGE2 has a role in IL-22 induction and development of ACD, which has increased prevalence in patients with AD...
June 3, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28569761/chemically-induced-mouse-models-of-acute-and-chronic-intestinal-inflammation
#17
Stefan Wirtz, Vanessa Popp, Markus Kindermann, Katharina Gerlach, Benno Weigmann, Stefan Fichtner-Feigl, Markus F Neurath
Inflammatory bowel diseases (IBDs) result in diarrhea and abdominal pain with further potential complications such as tissue fibrosis and stenosis. Animal models help in understanding the immunopathogenesis of IBDs and in the design of novel therapeutic concepts. Here we present an updated version of a protocol we published in 2007 for key models of acute and chronic forms of colitis induced by 2,4,6-trinitro-benzene sulfonic acid (TNBS), oxazolone and dextran sulfate sodium (DSS). This protocol update describes an adaptation of the existing protocol that modifies the technique...
July 2017: Nature Protocols
https://www.readbyqxmd.com/read/28505514/tlr4-supports-the-expansion-of-fasl-cd5-cd1d-hi-regulatory-b-cells-which-decreases-in-contact-hypersensitivity
#18
Keng Wang, Lei Tao, Jianbing Su, Yueyang Zhang, Binhua Zou, Yiyuan Wang, Min Zou, Nana Chen, Linsheng Lei, Xiaojuan Li
Certain B cells termed as "regulatory B cells" (Bregs) can suppress the ongoing immune responses and a splenic CD5(+)CD1d(hi) Breg subset identified earlier was shown to exert its regulatory functions through secretion of IL-10. Though FasL expression is an alternative mechanism of immune suppression used by B cells, little is known about the FasL expressing CD5(+)CD1d(hi) Bregs. In this study, we isolated splenocytes or splenic CD19(+) B cells and compared the efficiency of toll-like receptor(TLR)4 ligand (lipopolysaccharide) with TLR9 ligand (CpG), anti-CD40 and TLR9 ligand (CpG) plus anti-CD40 on the FasL expression of splenic CD5(+)CD1d(hi) Bregs by flow cytometry...
July 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28500957/design-synthesis-of-novel-oxazolone-triazinone-derivatives-and-their-biological-evaluation-as-cox-2-inhibitors
#19
Lamia W Mohamed, Osama M El-Badry, Afaf K El-Ansary, Ahmed Ismael
A new series of oxazolones and triazinones were designed and synthesized and evaluated against both COX-1 and COX-2 enzymes. Full structure elucidation of the new derivatives was performed using microanalyses, IR, 1H NMR, 13C NMR and mass spectra. Most of the derivatives showed good inhibitory activity against COX-2 enzyme specifically compounds IIIc, IIIe, IVd and IVg with IC50 values 0.024, 0.019, 0.011 and 0.014µM compared to celecoxib as reference drug with IC50 value of 0.05µM. Altogether, these results indicate that these derivatives can be effective anti-inflammatory agents...
June 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28482341/indigo-naturalis-ameliorates-oxazolone-induced-dermatitis-but-aggravates-colitis-by-changing-the-composition-of-gut-microflora
#20
Soichiro Adachi, Namiko Hoshi, Jun Inoue, Eiichiro Yasutomi, Takafumi Otsuka, Ramesh Dhakhwa, Zi Wang, Yuna Koo, Toshihiro Takamatsu, Yuriko Matsumura, Haruka Yamairi, Daisuke Watanabe, Makoto Ooi, Toshihito Tanahashi, Shin Nishiumi, Masaru Yoshida, Takeshi Azuma
BACKGROUND: Indigo naturalis (IND) is an herbal medicine that has been used as an anti-inflammatory agent to treat diseases including dermatitis and inflammatory bowel disease in China. However, the mechanism by which IND exerts its immunomodulatory effect is not well understood. METHODS: A murine model of dermatitis and inflammatory bowel disease, both induced by oxazolone (OXA), was treated with IND. The severity of dermatitis was evaluated based on ear thickness measurements and histological scoring...
2017: International Archives of Allergy and Immunology
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