Characterization of STING mediated innate immune sensing in the context of pathology

Download

index.pdf

Date

2018

Author

Şanlı, Hatice Asena

Metadata

Show full item record

Item Usage Stats

276
views

123
downloads

Type I interferonopathies are a group of diseases characterized by excess type I interferon production. Here, we examined the intracellular signal transduction pathways of two interferonopathies, STING-associated vasculopathy with Onset in Infancy (SAVI) and Aicardi-Goutières syndrome (AGS) using in vitro cell line models. SAVI is characterized by constitutive STING activation. M155V and N154S gain-of-function mutations in STING can cause disease in humans. We expressed the M155V mutant STING in STING-knocked out B16 Blue interferon reporter cell line. The effect of STING in tumor progression was investigated in mice using wild type, STING-/- or STINGM155V expressing B16 melanoma cells, with no significant differences between these groups. Using the STINGM155V expressing cells, we investigated type I IFN secretion profile to delineate the mechanism behind the cold-induced exacerbation of inflammation observed in SAVI patients. Similarly, TREX1 KO THP cells were used as a model of Aicardi-Goutières syndrome. Exposure to cold upregulated both p-STING and total STING levels in B16 cells, which may account for cold-temperature associated increase in inflammation in patients. Next, we analyzed the type I IFN suppressing activity of various inhibitors in our cell-line disease models. Results indicated that TBK1/IKK inhibitors Amlexanox and BX-795 were more effective in controlling chronic type I IFN production than the JAK/STAT inhibitors ruxolitinib and tofacitinib. Finally, we also investigated whether or not cGAS/STING signaling is regulated by circadian rhythms. Preliminary data showed that cGAS/STING-dependent type I IFN production oscillated over time, suggesting that this signaling pathway might indeed be under circadian regulation.

Subject Keywords

Interferon., Sting (Anatomy), Immunity., Cellular immunity.

URI

http://etd.lib.metu.edu.tr/upload/12622420/index.pdf
https://hdl.handle.net/11511/27437

Collections

Graduate School of Natural and Applied Sciences, Thesis

Suggestions

OpenMETU
Core

Investigation of diabetes-induced effect on apex of rat heart myocardium by using cluster analysis and neural network approach: An FTIR study Toyran, Neslihan; Severcan, Feride; Severcan, Mete; Turan, Belma (Hindawi Limited, 2007) Diabetes mellitus (DM) is a progressive chronic disorder, which affects people belonging to all age groups of the population. This disease is accompanied by a greatly increased risk of cardiovascular death. In the present study, the effects of streptozotocin (STZ)-induced type 1 diabetes on apex myocardium of the rat heart have been investigated using Fourier Transform Infrared (FTIR) spectra. The cluster analysis has been applied to FTIR spectra to differentiate the diabetic samples from the normal control...
Regulation of Glutathione S-Transferase Mu with type 1 diabetes and its regulation with antioxidants SADİ, GÖKHAN; Kartal, Deniz Irtem; Güray, Nülüfer Tülün (2013-01-01) Objective: Increased oxidative stress is now related with the pathogenesis and the chronic complications associated with the disease, diabetes mellitus. While roles of oxidative stress in diabetic complications are widely studied, the molecular mechanisms playing role in the regulations of detoxification enzymes in the presence of antioxidants have not been clearly established because of the complexity of the pathways.
Investigation of the Ligand Binding Characteristics of Staphylococcus aureus NorA Efflux Pump Işık , Esra Büşra; Serçinoğlu, Onur (Orta Doğu Teknik Üniversitesi Enformatik Enstitüsü; 2022-10) Staphylococcus aureus is a gram-positive bacterial pathogen which is highly adaptive to environmental conditions and causes various disorders. Excessive usage of antibiotics may result in development of antibiotic resistance in S. aureus. One of the resistance mechanisms is increase in the activity of transmembrane multi-drug efflux pumps. NorA is the most studied efflux pump in S. aureus, which belongs to Major Facilitator Superfamily (MFS). NorA has been shown to contribute to resistance against a variety...
Characterization of leishmania RNA virus infected leishmania major exosomes and evaluation of the impact of cytosolic DNA sensing related pathways in L. Major infection Yılmaz, İsmail Cem; Gürsel, Mayda; Department of Biology (2020) Leishmaniasis is a neglected infectious disease caused by Leishmaniaparasite. The disease represents a significant health problem, necessitating urgent development of effective treatment strategies. New World Leishmaniaspecies harboringLeishmania RNA virus (LRV) causesevere,metastatic disease. In this thesis, we compared LRV2-1 deficient and proficient Old World L. majorstrains in terms of their exosomal content and infectivity. PCR and mass spectrometry based analysis revealed that virus infectedLeishm...
Production of recombinant proteins by yeast cells Celik, Eda; Çalık, Pınar (Elsevier BV, 2012-09-01) Yeasts are widely used in production of recombinant proteins of medical or industrial interest. For each individual product, the most suitable expression system has to be identified and optimized, both on the genetic and fermentative level, by taking into account the properties of the product, the organism and the expression cassette. There is a wide range of important yeast expression hosts including the species Saccharomyces cerevisiae, Pichia pastoris, Hansenula polymorpha, Kluyveromyces lactis, Schizosa...

Citation Formats

H. A. Şanlı, “Characterization of STING mediated innate immune sensing in the context of pathology,” M.S. - Master of Science, Middle East Technical University, 2018.