Nanostructured DHA suppresses inflammatory activation in BV-2 microglial cells stimulated with E. coli

Introduction: Microglia are immune system cells that reside in the Central Nervous System (CNS), maintaining homeostasis and neurological function. During sepsis, in which the body mounts a dysregulated and exaggerated systemic response to infection, microglia alter their phenotype through the expression of Pattern Recognition Receptors (PRRs), releasing cytokines such as tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) (Annu Rev Immunol (2017) 35:441). To reduce complications associated with inflammatory processes, omega-3 has been studied as a therapeutic alternative due to its anti-inflammatory properties. Docosahexaenoic acid (DHA) is an omega-3 ligand of the Peroxisome Proliferator-Activated Receptors, which inhibit activation of nuclear factor kappa B (NF-kB), suppressing nuclear translocation of p65 thereby preventing the expression of pro-inflammatory genes. Nanostructures allow lipophilic drugs to be released by diffusion to act in the CNS, increasing its efficacy and bioavailability (Biomed Pharmacother (2023) 167:115474). We evaluated the effects of nanostructured DHA (nano DHA) in BV-2 microglial cells stimulated with Escherichia coli (E.coli) in neuroinflammation. Methods: BV-2 cells were pretreated with nano DHA at 1 and 10μM for 1h and stimulated with E. coli at MOI (multiplicity of infection) 10. After 24h, the resazurin assay was performed. The supernatant was collected to evaluate TNF-α and IL-6 by ELISA, or the cells were fixed for the immunocytochemistry assay to evaluate p65. Results: Viability showed that all experimental groups remained highly viable. Stimulation with E.coli increased the production of TNF-a and IL-6, while treatment with 10μM nano DHA reduced the level of TNF-a (p<0.05). Treatment with nano DHA reduced the nuclear translocation of the p65 protein. Conclusion: Nano DHA attenuated the pro-inflammatory effects in BV-2 stimulated with E. coli, indicating a reduction in neuroinflammation through the inhibition of NF-κB.