IL-4/ IL-13 directed microglial activation and differentiation in response to LPS-induced neuroinflammation
- Authors: Ackerdien, Shiraz
- Date: 2024-04
- Subjects: Inflammation , Inflammation -- Treatment , Anti-inflammatory agents
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10948/63606 , vital:73554
- Description: Microglia activation is a common hallmark of neuroinflammation that occurs during pathogen invasion or lipopolysaccharide (LPS)-induced inflammation. A neuroinflammatory response is elicited by the release of proinflammatory cytokines which stimulates microglia in an autocrine manner to be polarized into classically activated, pro-inflammatory M1 cells. Prolonged exposure to the inflammatory response can have disastrous effects on the central nervous system (CNS). However, microglia can alternatively be polarized into the activated M2 anti-inflammatory phenotype, but the exact molecular mechanism mediating this phenotypic switch remains poorly understood. Studies have shown that interleukin (IL)-4 can induce the M2 phenotype and activate the signal transducer and activator of the transcription 6 (STAT6) signalling pathway that in turn provokes a beneficial Th2 immune response. Since IL-4 and IL-13 share a common IL-4 receptor alpha (IL-4Rα) chain, it is possible that alternative microglia differentiation and its anti-inflammatory action also involve IL-13. This study aimed to investigate how IL-13 and STAT6 signalling orchestrates the microglial response and differentiation associated with LPS-induced inflammation. Furthermore, the molecular mechanisms that relieve LPS-induced neuroinflammation and neural protection through IL-13-enhanced BDNF signalling were also investigated. C8-B4 microglial cells were induced with LPS to exhibit an M1 pro-inflammatory phenotype or stimulated with IL-4 and/or IL-13 to exhibit an M2 anti-inflammatory microglial phenotype. The cell viability following LPS, IL-4, and/ or IL-13 exposure was determined. The LPS-induced neuroinflammatory response and the anti-inflammatory response induced by IL-4 and IL-13 which promotes STAT-6 signalling were determined by measuring TNFα, IL-1β, and BDNF protein concentrations using ELISA assays. The polarising effects of LPS and IL-4/IL-13 cytokines were also examined via changes in the expression of Iba-1, CD206, CD86, and STAT-6 determined by immunofluorescence analysis. These changes were further investigated by quantifying the mRNA transcripts of TNFα, IL-1 β, Arg-1, CD206, IL-4R, and STAT-6 and BDNF using qRT-PCR. , Thesis (MSc) -- Faculty of Science, School of Biomolecular & Chemical Sciences, 2024
- Full Text:
- Date Issued: 2024-04
- Authors: Ackerdien, Shiraz
- Date: 2024-04
- Subjects: Inflammation , Inflammation -- Treatment , Anti-inflammatory agents
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10948/63606 , vital:73554
- Description: Microglia activation is a common hallmark of neuroinflammation that occurs during pathogen invasion or lipopolysaccharide (LPS)-induced inflammation. A neuroinflammatory response is elicited by the release of proinflammatory cytokines which stimulates microglia in an autocrine manner to be polarized into classically activated, pro-inflammatory M1 cells. Prolonged exposure to the inflammatory response can have disastrous effects on the central nervous system (CNS). However, microglia can alternatively be polarized into the activated M2 anti-inflammatory phenotype, but the exact molecular mechanism mediating this phenotypic switch remains poorly understood. Studies have shown that interleukin (IL)-4 can induce the M2 phenotype and activate the signal transducer and activator of the transcription 6 (STAT6) signalling pathway that in turn provokes a beneficial Th2 immune response. Since IL-4 and IL-13 share a common IL-4 receptor alpha (IL-4Rα) chain, it is possible that alternative microglia differentiation and its anti-inflammatory action also involve IL-13. This study aimed to investigate how IL-13 and STAT6 signalling orchestrates the microglial response and differentiation associated with LPS-induced inflammation. Furthermore, the molecular mechanisms that relieve LPS-induced neuroinflammation and neural protection through IL-13-enhanced BDNF signalling were also investigated. C8-B4 microglial cells were induced with LPS to exhibit an M1 pro-inflammatory phenotype or stimulated with IL-4 and/or IL-13 to exhibit an M2 anti-inflammatory microglial phenotype. The cell viability following LPS, IL-4, and/ or IL-13 exposure was determined. The LPS-induced neuroinflammatory response and the anti-inflammatory response induced by IL-4 and IL-13 which promotes STAT-6 signalling were determined by measuring TNFα, IL-1β, and BDNF protein concentrations using ELISA assays. The polarising effects of LPS and IL-4/IL-13 cytokines were also examined via changes in the expression of Iba-1, CD206, CD86, and STAT-6 determined by immunofluorescence analysis. These changes were further investigated by quantifying the mRNA transcripts of TNFα, IL-1 β, Arg-1, CD206, IL-4R, and STAT-6 and BDNF using qRT-PCR. , Thesis (MSc) -- Faculty of Science, School of Biomolecular & Chemical Sciences, 2024
- Full Text:
- Date Issued: 2024-04
Investigating the anti-inflammatory effect of blueberry-AuNP on microglial cells and obese rat brains
- Authors: Ngwato, Anacia
- Date: 2024-04
- Subjects: Anti-inflammatory agents , Brain -- Anatomy , Brain -- Physiology
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10948/64266 , vital:73670
- Description: Nanotoxicology is a field of study that investigates how nanomaterials interact with biological systems. It focuses on understanding the correlation between the physicochemical properties of nanomaterials, such as size and stability, and their potential toxic effects. Gold nanoparticles (AuNPs), for instance, have a variety of applications in the biological sciences. Therefore, there is a great deal of attention given to evaluating their toxicity to ensure their safe and effective use in biological systems. Anti-inflammatory AuNPs have shown to be a desirable application in obesity treatments since obesity is associated with systematic inflammation. Thus, the study aimed to evaluate the anti-inflammatory effect of BE-AuNPs on C8-B4 microglial cell lines and, to validate the results, the grey matter of brain tissue of obese rats treated with BE-AuNPs. Following the synthesis and characterization of BE-AuNPs, C8-B4 microglial cells were treated with the BE-AuNPs and were evaluated through MTT, HRTEM imaging, qPCR, and ROS. LPS was used to activate the cells. Concentration-dependent toxicity of BE-AuNPs and cellular uptake was observed. The qPCR results showed that the BE-AuNPs decreased the LPS-induced inflammation in the cells. The BE-AuNPs were shown to reduce ROS in inflammatory conditions in the cells. Rat brain tissue analysis through qPCR and ROS demonstrated that BE-AuNPs reduce HFD-induced inflammation and had no ROS effects on the brain, respectively. Thus, leading to a conclusion the BE-AuNPs used in this study are anti-inflammatory. , Thesis (MSc) -- Faculty of Science, Biomolecular & Chemical Sciences, 2024
- Full Text:
- Date Issued: 2024-04
- Authors: Ngwato, Anacia
- Date: 2024-04
- Subjects: Anti-inflammatory agents , Brain -- Anatomy , Brain -- Physiology
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10948/64266 , vital:73670
- Description: Nanotoxicology is a field of study that investigates how nanomaterials interact with biological systems. It focuses on understanding the correlation between the physicochemical properties of nanomaterials, such as size and stability, and their potential toxic effects. Gold nanoparticles (AuNPs), for instance, have a variety of applications in the biological sciences. Therefore, there is a great deal of attention given to evaluating their toxicity to ensure their safe and effective use in biological systems. Anti-inflammatory AuNPs have shown to be a desirable application in obesity treatments since obesity is associated with systematic inflammation. Thus, the study aimed to evaluate the anti-inflammatory effect of BE-AuNPs on C8-B4 microglial cell lines and, to validate the results, the grey matter of brain tissue of obese rats treated with BE-AuNPs. Following the synthesis and characterization of BE-AuNPs, C8-B4 microglial cells were treated with the BE-AuNPs and were evaluated through MTT, HRTEM imaging, qPCR, and ROS. LPS was used to activate the cells. Concentration-dependent toxicity of BE-AuNPs and cellular uptake was observed. The qPCR results showed that the BE-AuNPs decreased the LPS-induced inflammation in the cells. The BE-AuNPs were shown to reduce ROS in inflammatory conditions in the cells. Rat brain tissue analysis through qPCR and ROS demonstrated that BE-AuNPs reduce HFD-induced inflammation and had no ROS effects on the brain, respectively. Thus, leading to a conclusion the BE-AuNPs used in this study are anti-inflammatory. , Thesis (MSc) -- Faculty of Science, Biomolecular & Chemical Sciences, 2024
- Full Text:
- Date Issued: 2024-04
A study of the rabbit eye test system to determine the activity of acidic non-steroidal anti-inflammatory agents
- Authors: Wiseman, Ian Charles
- Date: 1977
- Subjects: Nonsteroidal anti-inflammatory agents , Anti-inflammatory agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3855 , http://hdl.handle.net/10962/d1013276
- Description: From introduction : "Inflammation per se, has been defined sufficiently to permit a rational approach to the search for drugs that modify this process, but satisfactory animal models for most rheumatoid diseases are not available". (Swingle 1974) In the search for new meaningful procedures for the detection and evaluation of anti-inflammatory drugs, the rabbit eye as a test system was studied.
- Full Text:
- Date Issued: 1977
- Authors: Wiseman, Ian Charles
- Date: 1977
- Subjects: Nonsteroidal anti-inflammatory agents , Anti-inflammatory agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3855 , http://hdl.handle.net/10962/d1013276
- Description: From introduction : "Inflammation per se, has been defined sufficiently to permit a rational approach to the search for drugs that modify this process, but satisfactory animal models for most rheumatoid diseases are not available". (Swingle 1974) In the search for new meaningful procedures for the detection and evaluation of anti-inflammatory drugs, the rabbit eye as a test system was studied.
- Full Text:
- Date Issued: 1977
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