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https://www.readbyqxmd.com/read/27914477/in-vitro-rescue-of-genital-strains-of-chlamydia-trachomatis-from-interferon-%C3%AE-and-tryptophan-depletion-with-indole-positive-but-not-indole-negative-prevotella-spp
#1
Noa Ziklo, Wilhelmina M Huston, Kuong Taing, Mohammad Katouli, Peter Timms
BACKGROUND: The natural course of sexually transmitted infections caused by Chlamydia trachomatis varies between individuals. In addition to parasite and host effects, the vaginal microbiota might play a key role in the outcome of C. trachomatis infections. Interferon-gamma (IFN-γ), known for its anti-chlamydial properties, activates the expression of indoleamine 2,3-dioxygenase (IDO1) in epithelial cells, an enzyme that catabolizes the amino acid L- tryptophan into N-formylkynurenine, depleting the host cell's pool of tryptophan...
December 3, 2016: BMC Microbiology
https://www.readbyqxmd.com/read/27910911/human-mesenchymal-stem-cells-program-macrophage-plasticity-by-altering-their-metabolic-status-via-a-pge2-dependent-mechanism
#2
Anoop Babu Vasandan, Sowmya Jahnavi, Chandanala Shashank, Priya Prasad, Anujith Kumar, S Jyothi Prasanna
Mesenchymal stem cells (MSCs) are speculated to act at macrophage-injury interfaces to mediate efficient repair. To explore this facet in-depth this study evaluates the influence of MSCs on human macrophages existing in distinct functional states. MSCs promoted macrophage differentiation, enhanced respiratory burst and potentiated microbicidal responses in naïve macrophages (Mφ). Functional attenuation of inflammatory M1 macrophages was associated with a concomitant shift towards alternatively activated M2 state in MSC-M1 co-cultures...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27906184/1-methyl-tryptophan-attenuates-regulatory-t-cells-differentiation-due-to-the-inhibition-of-estrogen-ido1-mrc2-axis-in-endometriosis
#3
Chunyan Wei, Jie Mei, Lingli Tang, Yukai Liu, Dajin Li, Mingqing Li, Xiaoyong Zhu
Foxp3(+) regulatory T (Treg) cells contribute to the local dysfunctional immune environment in endometriosis, an estrogen-dependent gynecological disease, which affects the function of ectopic endometrial tissue clearance by the immune system. The reason for the high percentage of peritoneal Treg in endometriosis patients is unknown. Here, we show that the proportion of peritoneal Treg cells increases as endometriosis progresses. To determine the probable mechanism, we established a naive T cell-macrophage-endometrial stromal cell (ESC) co-culture system to mimic the peritoneal cavity microenvironment...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27891058/ido2-a-pathogenic-mediator-of-inflammatory-autoimmunity
#4
REVIEW
Lauren M F Merlo, Laura Mandik-Nayak
Indoleamine 2,3-dioxygenase 2 (IDO2), a homolog of the better-studied tryptophan-catabolizing enzyme IDO1, is an immunomodulatory molecule with potential effects on various diseases including cancer and autoimmunity. Here, we review what is known about the direct connections between IDO2 and immune function, particularly in relationship to autoimmune inflammatory disorders such as rheumatoid arthritis and lupus. Accumulating evidence indicates that IDO2 acts as a pro-inflammatory mediator of autoimmunity, with a functional phenotype distinct from IDO1...
2016: Clinical Medicine Insights. Pathology
https://www.readbyqxmd.com/read/27889479/ido1-is-an-integral-mediator-of-inflammatory-neovascularization
#5
Arpita Mondal, Courtney Smith, James B DuHadaway, Erika Sutanto-Ward, George C Prendergast, Arturo Bravo-Nuevo, Alexander J Muller
The immune tolerogenic effects of IDO1 (indoleamine 2,3-dioxygenase 1) have been well documented and genetic studies in mice have clearly established the significance of IDO1 in tumor promotion. Dichotomously, the primary inducer of IDO1, the inflammatory cytokine IFNγ (interferon-γ), is a key mediator of immune-based tumor suppression. One means by which IFNγ can exert an anti-cancer effect is by decreasing tumor neovascularization. We speculated that IDO1 might contribute to cancer promotion by countering this anti-neovascular effect of IFNγ, possibly through IDO1-potentiated elevation of the pro-tumorigenic inflammatory cytokine IL6 (interleukin-6)...
November 9, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27877172/regulated-inflammation-and-lipid-metabolism-in-colon-mrna-expressions-of-obese-germfree-mice-responding-to-enterobacter-cloacae-b29-combined-with-the-high-fat-diet
#6
Huiying Yan, Na Fei, Guojun Wu, Chenhong Zhang, Liping Zhao, Menghui Zhang
Increased evidences have demonstrated that gut microbiota targeted diet intervention can alleviate obesity and related metabolic disorders. The underlying mechanism of interactions among diet, microbiota, and host still remains unclear. Enterobacter cloacae B29, an endotoxin-producing strain dominated in the gut of a morbidly obese volunteer (weight 174.8 kg, BMI 58.8 kg m(-2)) was isolated and transplanted to germfree mice (inoculated 10(10) cells of B29 per day for 1 week). Using deep mRNA sequencing technology, we compared different gene expression profiles in the colon samples of the germfree mice treated with/without B29 and/or high fat diet (HFD) for 16 weeks and identified 279 differential expressed genes in total, including up-regulated genes Apoa4 (fold change, 2...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27863031/discovery-of-a-novel-scaffold-as-an-indoleamine-2-3-dioxygenase%C3%A2-1-ido1-inhibitor-based-on-the-pyrrolopiperazinone-alkaloid-longamide%C3%A2-b
#7
Zenyu Shiokawa, Emi Kashiwabara, Daisuke Yoshidome, Koichi Fukase, Shinsuke Inuki, Yukari Fujimoto
Indoleamine 2,3-dioxygenase 1 (IDO1) has emerged as a key target for cancer therapy, as IDO1 plays a critical role in the capacity of tumor cells to evade the immune system. The pyrrolopiperazinone alkaloid longamide B and its derivatives were identified as novel IDO1 inhibitors based on docking studies and small library synthesis. The thioamide derivative showed higher IDO1 inhibitory activity than longamide B, and displayed an activity similar to that of a representative IDO1 inhibitor, 1-methyl-tryptophan...
November 11, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27860276/regulation-of-kynurenine-biosynthesis-during-influenza-virus-infection
#8
Lana Gaelings, Sandra Söderholm, Andrii Bugai, Yu Fu, Jatin Nandania, Bert Schepens, Martina B Lorey, Janne Tynell, Liesbeth Vande Ginste, Ronan Le Goffic, Matthew S Miller, Marika Kuisma, Varpu Marjomäki, Jef De Brabander, Sampsa Matikainen, Tuula A Nyman, Dennis Bamford, Xavier Saelens, Ilkka Julkunen, Henrik Paavilainen, Veijo Hukkanen, Vidya Velagapudi, Denis E Kainov
Influenza A viruses (IAVs) remain serious threats to public health because of the shortage of effective means of control. Developing more effective virus control modalities requires better understanding of virus-host interactions. It has previously been shown that IAV induces the production of kynurenine, which suppresses T-cell responses, enhances pain hypersensitivity and disturbs behaviour in infected animals. However, the regulation of kynurenine biosynthesis during IAV infection remains elusive. Here we showed that IAV infection induced expression of interferons (IFNs), which upregulated production of indoleamine-2,3-dioxygenase (IDO1), which catalysed the kynurenine biosynthesis...
November 18, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27828964/chronic-treatment-with-the-ido1-inhibitor-1-methyl-d-tryptophan-minimizes-the-behavioural-and-biochemical-abnormalities-induced-by-unpredictable-chronic-mild-stress-in-mice-comparison-with-fluoxetine
#9
Anthony Laugeray, Jean-Marie Launay, Jacques Callebert, Oguz Mutlu, Gilles J Guillemin, Catherine Belzung, Pascal R Barone
We demonstrated that confronting mice to the Unpredictable Chronic Mild Stress (UCMS) procedure-a validated model of stress-induced depression-results in behavioural alterations and biochemical changes in the kynurenine pathway (KP), suspected to modify the glutamatergic neurotransmission through the imbalance between downstream metabolites such as 3-hydroxykynurenine, quinolinic and kynurenic acids. We showed that daily treatment with the IDO1 inhibitor 1-methyl-D-tryptophan partially rescues UCMS-induced KP alterations as does the antidepressant fluoxetine...
2016: PloS One
https://www.readbyqxmd.com/read/27819068/the-kynurenine-tryptophan-ratio-and-glioblastoma-patients-treated-with-hsppc-96-vaccine
#10
Alicia Lenzen, Lijie Zhai, Kristen L Lauing, Galina Gritsina, Erik Ladomersky, Matthew Genet, C David James, Orin Bloch, Derek A Wainwright
The discovery that immunotherapy is a clinically-relevant approach for the treatment of malignant tumors is revolutionizing patient care. In adults diagnosed with glioblastoma (GBM), an aggressive and incurable primary brain tumor, autologous HSPPC-96 vaccination provides a significant increase in overall survival. However, all GBM patients eventually succumb to their disease, providing rationale for discovering new methods that proactively identify individuals that will respond, optimally. Of the immunosuppressive mediators that contribute to the inhibition of productive tumor immunity, indoleamine 2,3 dioxygenase 1 (IDO1), a rate-limiting enzyme that catabolizes tryptophan (Trp) into kynurenine (Kyn), has been demonstrated to be expressed at elevated levels in patients with malignant glioma...
September 2016: Immunotherapy (Los Angeles, Calif.)
https://www.readbyqxmd.com/read/27799931/immunomodulatory-factors-galectin-9-and-interferon-gamma-synergize-to-induce-expression-of-rate-limiting-enzymes-of-the-kynurenine-pathway-in-the-mouse-hippocampus
#11
Alexandra K Brooks, Marcus A Lawson, Jennifer L Rytych, Kevin C Yu, Tiffany M Janda, Andrew J Steelman, Robert H McCusker
Elevated levels of circulating pro-inflammatory cytokines are associated with symptomology of several psychiatric disorders, notably major depressive disorder. Symptomology has been linked to inflammation/cytokine-dependent induction of the Kynurenine Pathway. Galectins, like pro-inflammatory cytokines, play a role in neuroinflammation and the pathogenesis of several neurological disorders but without a clearly defined mechanism of action. Their involvement in the Kynurenine Pathway has not been investigated...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27769672/discovery-and-preliminary-structure-activity-relationship-of-1h-indazoles-with-promising-indoleamine-2-3-dioxygenase-1-ido1-inhibition-properties
#12
Shan Qian, Tao He, Wei Wang, Yanying He, Man Zhang, Lingling Yang, Guobo Li, Zhouyu Wang
Indoleamine 2,3-dioxygenase 1 (IDO1)-mediated kynurenine pathway of tryptophan degradation is identified as an important immune effector pathway in the tumor cells to escape a potentially effective immune response. IDO1 is an attractive target for anticancer therapy and the discovery of IDO1 inhibitors has been intensely ongoing in both academic research laboratories and pharmaceutical organizations. Our study discovered that 1H-indazole was a novel key pharmacophore with potent IDO1 inhibitory activity. A series of new 1H-indazole derivatives were synthesized and determined the enzyme inhibitory activities, and the compound 2g exhibited the highest activity with an IC50 value of 5...
October 6, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27769618/novel-substituted-hydrazono-indolo-2-1-b-quinazoline-6-12-dione-analogues-as-cytostatic-agents-synthesis-crystal-structure-biological-evaluation-and-molecular-docking-studies
#13
Ramu Guda, Sirassu Narsimha, Ramavath Babu, Srujana Muthadi, Harikiran Lingabathula, Rambabu Palabindela, Narsimha Reddy Yellu, Girijesh Kumar, Mamatha Kasula
A series of novel substituted hydrazono indolo[2,1-b]quinazoline-6,12-dione analogues have been synthesized and screened for their in vitro cytotoxic and antimicrobial activities. Among all the target compounds, 3c exhibited the most potent inhibitory activity against three cancer cell lines MCF-7, A549, HeLa with IC50 values 07.14±1.285μM, 09.18±0.968μM and 10.57±0.581μM respectively, while maintaining low toxicity towards non-cancer originated cell line, HEK-293. The detailed studies about molecular interactions with probable target protein indoleamine 2,3-dioxygenase (IDO1) were done by using docking simulations...
October 5, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27696702/distinct-roles-of-immunoreceptor-tyrosine-based-motifs-in-immunosuppressive-indoleamine-2-3-dioxygenase-1
#14
Elisa Albini, Verdiana Rosini, Marco Gargaro, Giada Mondanelli, Maria L Belladonna, Maria Teresa Pallotta, Claudia Volpi, Francesca Fallarino, Antonio Macchiarulo, Cinzia Antognelli, Roberta Bianchi, Carmine Vacca, Paolo Puccetti, Ursula Grohmann, Ciriana Orabona
The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) catalyses the initial, rate-limiting step in tryptophan (Trp) degradation, resulting in tryptophan starvation and the production of immunoregulatory kynurenines. IDO1's catalytic function has long been considered as the one mechanism responsible for IDO1-dependent immune suppression by dendritic cells (DCs), which are master regulators of the balance between immunity and tolerance. However, IDO1 also harbours immunoreceptor tyrosine-based inhibitory motifs, (ITIM1 and ITIM2), that, once phosphorylated, bind protein tyrosine phosphatases, (SHP-1 and SHP-2), and thus trigger an immunoregulatory signalling in DCs...
September 30, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27695641/cell-intrinsic-factors-modulate-the-effects-of-ifn%C3%AE-on-the-development-of-chlamydia-trachomatis
#15
Shardulendra Sherchand, Joyce A Ibana, Alison J Quayle, Ashok Aiyar
Chlamydia trachomatis is an obligate intracellular bacterial pathogen that cannot synthesize several amino acids, including tryptophan. Rather, C. trachomatis acquires these essential metabolites from its human host cell. Chlamydial dependence on host-provided tryptophan underlies a major host defense mechanism against the bacterium; namely, the induction of the host tryptophan-catabolizing enzyme, indoleamine 2,3- dioxygenase (IDO1) by interferon gamma (IFNγ), which leads to eradication of C. trachomatis by tryptophan starvation...
August 2016: Journal of Bacteriology & Parasitology
https://www.readbyqxmd.com/read/27690429/new-inhibitors-of-indoleamine-2-3-dioxygenase-1-molecular-modelling-studies-synthesis-and-biological-evaluation
#16
Antonio Coluccia, Sara Passacantilli, Valeria Famiglini, Manuela Sabatino, Alexandros Patsilinakos, Rino Ragno, Carmela Mazzoccoli, Lorenza Sisinni, Alato Okuno, Osamu Takikawa, Romano Silvestri, Giuseppe La Regina
Indoleamine 2,3-dioxygenase 1 (IDO1) is an attractive target for anticancer therapy. Herein, we report a virtual screening study which led to the identification of compound 5 as a new IDO1 inhibitor. In order to improve the biological activity of the identified hit, arylthioindoles 6-30 were synthesized and tested. Among these, derivative 21 exhibited an IC50 value of 7 microM, being the most active compound of the series. Furthermore, compounds 5 and 21 induced a dose-dependent growth inhibition in IDO1 expressing cancer cell lines HTC116 and HT29...
October 3, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27689750/prolongation-of-kidney-allograft-survival-regulated-by-indoleamine-2-3-dioxygenase-in-immature-dendritic-cells-generated-from-recipient-type-bone-marrow-progenitors
#17
Ning Na, Yun Luo, Daqiang Zhao, Shicong Yang, Liangqing Hong, Heng Li, Bin Miao, Jiang Qiu
Immature dendritic cells (iDCs) are bone marrow-derived professional antigen-presenting cells, exhibit very low levels of the co-stimulatory molecules CD80 (B7-1), CD86 (B7-2), and CD40 and major histocompatibility complex (MHC) class II and play a critical role in triggering antigen-specific immunotolerance. The enzyme indoleamine 2, 3-dioxygenase (IDO) is a cytosolic tryptophan catabolism rate-limiting step enzyme. IDO secreted by DCs shows an association with the suppression of T-cell responses and promotion of tolerance...
September 27, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27672107/somatic-mutation-copy-number-and-transcriptomic-profiles-of-primary-and-matched-metastatic-estrogen-receptor-positive-breast-cancers
#18
D Fumagalli, T R Wilson, R Salgado, X Lu, J Yu, C O'Brien, K Walter, L Y Huw, C Criscitiello, I Laios, V Jose, D N Brown, F Rothé, M Maetens, D Zardavas, P Savas, D Larsimont, M J Piccart-Gebhart, S Michiels, M R Lackner, C Sotiriou, S Loi
BACKGROUND: Estrogen receptor-positive (ER+) breast cancers (BCs) constitute the most frequent BC subtype. The molecular landscape of ER+ relapsed disease is not well characterized. In this study, we aimed to describe the genomic evolution between primary (P) and matched metastatic (M) ER+ BCs after failure of adjuvant therapy. MATERIALS AND METHODS: A total of 182 ER+ metastatic BC patients with long-term follow-up were identified from a single institution. P tumor tissue was available for all patients, with 88 having matched M material...
October 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27668274/behavioral-and-cognitive-data-in-mice-with-different-tryptophan-metabolizing-enzymes-knocked-out
#19
Lay Khoon Too, Kong M Li, Cacang Suarna, Ghassan J Maghzal, Roland Stocker, Iain S McGregor, Nicholas H Hunt
This article demonstrates behavioral changes in mice in response to free adaptation and drinking session adaptation modules implemented in their social home environment, the IntelliCage. These data complement the study "Deletion of TDO2, IDO-1 and IDO-2 differentially affects mouse behavior and cognitive function" (Too LK, Li KM, Suarna C, Maghzal GJ, Stocker R, McGregor IS, et al., 2016) [1]. Prior to programmed drinking sessions, all mice were exposed to a home cage adaptation module during which there was no time limit on water access - the free adaptation module...
December 2016: Data in Brief
https://www.readbyqxmd.com/read/27647832/ido1-and-tgf-%C3%AE-mediate-protective-effects-of-ifn-%C3%AE-in-antigen-induced-arthritis
#20
Jaya Prakash Chalise, Maria Teresa Pallotta, Sudeep Chenna Narendra, Björn Carlsson, Alberta Iacono, Joanitah Namale, Louis Boon, Ursula Grohmann, Mattias Magnusson
IFN-α prevents Ag-induced arthritis (AIA), and in this study we investigated the role of IDO1 and TGF-β signaling for this anti-inflammatory property of IFN-α. Arthritis was induced by methylated BSA (mBSA) in mBSA-sensitized wild-type (WT), Ido1(-/-), or Ifnar(-/-) mice, treated or not with IFN-α or the IDO1 product kynurenine (Kyn). Enzymatic IDO1 activity, TGF-β, and plasmacytoid dendritic cells (pDC) were neutralized by 1-methyltryptophan and Abs against TGF-β and pDC, respectively. IDO1 expression was determined by RT-PCR, Western blot, and FACS, and enzymatic activity by HPLC...
September 19, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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