Effect of immunosuppressive oligodeoxynucleotide A151 on inflammasome activation pathways

Download
2017
Sürücü, Naz
Inflammasome activation is triggered by pathogen associated molecular patterns (PAMPs) and/or host derived danger associated molecular patterns (DAMPs) leading to caspase-1 (canonical) or caspase-11/caspase-4/5 activation (non-canonical) pathways stimulating IL-1β and IL-18 secretion. Excessive inflammasome activation has been associated with the pathogenesis of neurodegenerative and metabolic disorders as well as the macrophage activation syndrome (MAS) and cryopyrin associated periodic syndromes (CAPS). H syndrome, is another rare disease arising due to mutations in the genes encoding hENT3 (human equilibrative nucleoside transporter). This syndrome shares common symptoms with the inflammasome overactivation associated disorders CAPS and MAS which might suggest a common mechanistic origin of these diseases and the pathogenesis of H syndrome. The existence of these inflammasome overactivation related disorders necessitates the development of therapeutic agents targeting distinct pathways of inflammasome activation. Synthetic oligodeoxynucleotide (ODN) A151 expressing immunosuppressive TTAGGG motifs has been shown to ameliorate various inflammatory responses. In this study, we observed a significant decrease in IL-1β secretion and percent cytotoxicity of A151-ODN treated cells in AIM2, NLRC4, non-canonically activated, and nucleic acid induced NLRP3 inflammasomes but not in bacterial toxin stimulated NLRP3 inflammasome formation. Furthermore, we demonstrate a decrease in the release of ASC specks and inhibition of mitochondrial stress in A151 ODN treated samples. These are encouraging results for the potential therapeutic immunosuppressive effects of A151 ODN on dysregulated inflammasome complex formation. Finally, preliminary experiments using PBMC from an H syndrome patient suggested that autoinflammatory manifestations in this disease might in part be associated with over-active inflammasome formation. 

Suggestions

Effect of stereotactic radiosurgery on lipids and proteins of normal and hypoperfused rat brain homogenates: A Fourier transform infrared spectroscopy study
Toyran, N; Zorlu, F; Severcan, Feride (Informa UK Limited, 2005-12-01)
Purpose: The effect of stereotactic radiosurgery on lipids and proteins of normal and hypoperfused rat brain was investigated to see if hypoxic areas are really more resistant to radiation effects or not.
Effect of suppressive DNA on CpG-induced immune activation.
Yamada, H; Gursel, I; Takeshita, F; Conover, J; Ishii, KJ; Gürsel, Mayda; Takeshita, S; Klinman, DM (The American Association of Immunologists, 2002-11-15)
Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs stimulate a strong innate immune response. This stimulation can be abrogated by either removing the CpG DNA or adding inhibitory/suppressive motifs. Suppression is dominant over stimulation and is specific for CpG-induced immune responses (having no effect on LPS- or Con A-induced activation). Individual cells noncompetitively internalize both stimulatory and suppressive ODN. Studies using ODN composed of both stimula...
Effect of EDTA on activated sludge properties
Sanin, Faika Dilek (2001-02-01)
Bacterial extracellular polymers have been found to be important in bioflocculation of activated sludge. In this study ethylene diamine tetra acetic acid (EDTA) method of extracting bacterial extracellular polymers is examined. Following extractions, it is observed that EDTA extracted significant amounts of biopolymers. However, the chemical treatment causes serious changes in sludge properties. Sludge particle size is reduced from 21 mum to 14.6 mum, filtration properties of sludge deteriorates, indicated ...
Effects of human granulocyte-colony stimulating factor on fracture healing in rats
Bozlar, M; Aslan, B; Kalaci, A; Baktiroglu, L; Yanat, AN; Tasci, A (2005-08-01)
Objective: Granulocyte colony stimulation factor (G-CSF) is generally used to prevent and cure the neutropenia associated with chemotherapy and bone marrow transplantation. In addition to its effects on neutrophil function, G-CSF was found to have the characteristic of modulating the cytokines in the inflammatory response. Then, the question to answer is whether it has any effect on fracture healing and to what extent? In this study, we test the effects of G-CSF on the healing of tibia fracture in a rat model.
Effect of nitric acid for equal stabilization and sensitivity of different selenium species in electrothermal atomic absorption spectrometry
Sahin, F; Volkan, Mürvet; Ataman, Osman Yavuz (2005-08-15)
Determination of selenium by electrothermal atomic absorption spectrometry (ETAAS) is complicated by the presence of different species of this analyte. The presence of different oxidation states (-II, IV and VI) may result in different sensitivities obtained for each species rendering impossible the use of a single species for calibration. These species also exhibit different behaviours regarding thermal stabilities; the temperature program must be provided to conform to this problem. Chemical modifiers are...
Citation Formats
N. Sürücü, “Effect of immunosuppressive oligodeoxynucleotide A151 on inflammasome activation pathways,” M.S. - Master of Science, Middle East Technical University, 2017.