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Exploring the role of opioid signaling in modulation of microglial function
Mali, Akash Shivling ; Novotný, Jiří (advisor) ; Svoboda, Petr (referee) ; Machová Urdzíková, Lucia (referee)
Microglial activation is the most important component of neuroinflammation. It appears that opioids may affect microglial M1/M2 polarization in different ways depending on the type of receptor employed. In addition to opioid receptors, Toll-like receptor 4 (TLR4) of the innate immune system can also be activated by some opioid ligands and thus elicit specific cellular responses. Although opioid receptors (ORs) are known to regulate neurotransmission in various peptidergic neurons, their potential role in modulation of microglial function remains largely unknown. In this study, we investigated the effects of OR agonists, namely DAMGO, DADLE, and U-50488, on polarization and metabolic modulation of C8-B4 microglial cells. Our findings have revealed that opioids effectively suppress lipopolysaccharide (LPS)-triggered M1 polarization and promote the M2 polarization state. This was evidenced by decreased phagocytic activity, decreased production of nitric oxide (NO), diminished expression of proinflammatory cytokines such as TNF-α, IL-1β, IL-6, IL-86, and IL-12 beta p40, along with an increased migration rate and elevated expression of anti-inflammatory markers such as IL-4, IL-10, IL-13 arginase 1, and CD206 in microglia compared to cells influenced by LPS. Furthermore, we have demonstrated that...
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Signaling systems of TLR receptors in microglia
Prokop, Jonáš ; Novotný, Jiří (advisor) ; Filipp, Dominik (referee)
Emerging importance of TLR signalling in microglia has been suggested by various studies of neuroinflammation. Both MyD88 dependent and TRIF dependent pathways used by TLR induce secretion of proinflammatory cytokines in microglia by the activation of transcriptional factors such as NF-κB. This in turn polarizes the whole microglial population to a proinflammatory phenotype. Under physiological conditions microglia express various anti-inflammatory and growth factors and serve in the maintenance of the CNS. Once activated, microglia are connected to neuroinflammation and in the case of overactivation to neurodegeneration. Research of TLR signalling in microglial populations is important for our understanding of complex pathologies of the central nervous system. Moreover, exact knowledge of associated mechanisms might prove very useful in finding new therapeutic approaches. Key words: Microglia, signalling systems of toll-like receptors, Myd88, TRIF, neuroinflammation, neurodegeneration
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