miR-30a-5p Augments the Anti-inflammatory Effects of Dexmedetomidine in LPS-induced BV2 Cells
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Neuroinflammation is defined as a neurological inflammation within the brain and the spinal cord. In neuroinflammation, microglia are the tissue-resident macrophages of the central nervous system, which act as the first line of defense against harmful pathogens. Dexmedetomidine (Dex) has an anti-inflammatory effect in many neurological conditions. Additionally, the microRNA-30a-5p (miR-30a-5p) mimic has been proven to be effective in macrophages in inflammatory conditions. This study aimed to investigate the synergistic anti-inflammatory effects of both miR-30a-5p and Dex in lipopolysaccharide (LPS)-induced BV2 cells. This study showed that miR-30a-5p and Dex decreased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) translocation in LPS-induced BV2 cells. MiR-30a-5p and Dex alleviated tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), LPS-induced phosphorylation c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (ERK) and p38. Also, the expression of the NOD-like receptor pyrin domain containing 3 inflammasome (NLRP3), cleaved caspase-1, and ASC was inhibited. Furthermore, LPS-stimulated nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), and cyclooxygenase- 2 (COX-2) expression were attenuated by Dex and miR-30a-5p. Our results indicate that a combination of Dex and miR-30a-5p, attenuates NF-κB activation, the mitogen-activated protein kinase (MAPK) signaling pathway, and inflammatory mediators involved in LPS-induced inflammation and inhibits the activation of the NLRP3 inflammasome in LPS-activated BV2 cells.
Abstract
Neuroinflammation is defined as a neurological inflammation within the brain and the spinal cord. In neuroinflammation, microglia are the tissue-resident macrophages of the central nervous system, which act as the first line of defense against harmful pathogens. Dexmedetomidine (Dex) has an anti-inflammatory effect in many neurological conditions. Additionally, the microRNA-30a-5p (miR-30a-5p) mimic has been proven to be effective in macrophages in inflammatory conditions. This study aimed to investigate the synergistic anti-inflammatory effects of both miR-30a-5p and Dex in lipopolysaccharide (LPS)-induced BV2 cells. This study showed that miR-30a-5p and Dex decreased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) translocation in LPS-induced BV2 cells. MiR-30a-5p and Dex alleviated tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), LPS-induced phosphorylation c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (ERK) and p38. Also, the expression of the NOD-like receptor pyrin domain containing 3 inflammasome (NLRP3), cleaved caspase-1, and ASC was inhibited. Furthermore, LPS-stimulated nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), and cyclooxygenase- 2 (COX-2) expression were attenuated by Dex and miR-30a-5p. Our results indicate that a combination of Dex and miR-30a-5p, attenuates NF-κB activation, the mitogen-activated protein kinase (MAPK) signaling pathway, and inflammatory mediators involved in LPS-induced inflammation and inhibits the activation of the NLRP3 inflammasome in LPS-activated BV2 cells.
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