AGK-2 and resveratrol reduce pro-inflammatory cytokines in microglia stimulates with Klebsiella pneumoniae

Introduction: Under neurodegenerative conditions, microglial cells are activated and undergo morphological and physiological changes, producing pro-inflammatory factors such as tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) (1). Sepsis causes glial activation (2). Sepsis is characterized by a large production of cytokines, causing hemodynamic and metabolic problems (3). The presence of activated microglia and inflammation has also been described in sepsis and sepsis-associated encephalopathy (4). Sepsis can be caused by a microorganism, as in pneumonia induced by K. pneumoniae, opportunistic bacterium associated with antimicrobial resistance. (5). Sirtuins (SIRTs), belonging to the class III histone/lysine deacetylase family. SIRT1 has neuroprotection among its functions, an effect opposite to the neurodegeneration promoted by SIRT2 (6). Resveratrol is a pharmacological activator of SIRT1 (7). AGK2 is a potent inducer of SIRT1 and a selective inhibitor of SIRT2, resulting in antagonism of neuroinflammation and neurodegeneration (8). Objective: To analyze the effects of treatment with the SIRT modulators AGK-2 and resveratrol, evaluating the production of inflammatory cytokines IL-6 and TNF-α. Methods: Murine microglia (BV-2) were pretreated with resveratrol and AGK-2 and exposed to K. pneumoniae. The supernatant was collected after 24 hours for ELISA analysis of the cytokines IL-6 and TNF-α. Results and Conclusion: We suggest that resveratrol and AGK-2, significantly reduced pro-inflammatory cytokines in BV-2 cells stimulated with K. pneumoniae, demonstrating the anti-inflammatory potential of these drugs. References:

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