title: Folic Acid Is Able to Polarize the Inflammatory Response in LPS Activated Microglia by Regulating Multiple Signaling Pathways.
abstract: We investigated the ability of folic acid to modulate the inflammatory responses of LPS activated BV-2 microglia cells and the signal transduction pathways involved. To this aim, the BV-2 cell line was exposed to LPS as a proinflammatory response inducer, in presence or absence of various concentrations of folic acid. The production of nitric oxide (NO) was determined by the Griess test. The levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-10 were determined by ELISA. Inducible NO synthase (iNOS), nuclear transcription factor-kappa B (NF-κB) p65, MAPKs protein, and suppressors of cytokine signaling (SOCS)1 and SOCS3 were analyzed by western blotting. TNF-αand IL-1β, as well as iNOS dependent NO production, resulted significantly inhibited by folic acid pretreatment in LPS-activated BV-2 cells. We also observed that folic acid dose-dependently upregulated both SOCS1 and SOCS3 expression in BV-2 cells, leading to an increased expression of the anti-inflammatory cytokine IL-10. Finally, p-IκBα, which indirectly reflects NF-κB complex activation, and JNK phosphorylation resulted dose-dependently downregulated by folic acid pretreatment of LPS-activated cells, whereas p38 MAPK phosphorylation resulted significantly upregulated by folic acid treatment. Overall, these results demonstrated that folic acid was able to modulate the inflammatory response in microglia cells, shifting proinflammatory versus anti-inflammatory responses through regulating multiple signaling pathways.
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.
authors.forename: Antonia
authors.identifier: 0000-0002-9851-3124
authors.initials: A
authors.lastname: Cianciulli
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Salvatore
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Porro
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Trotta
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.
authors.forename: Maria Antonietta
authors.identifier: 0000-0001-5457-1069
authors.initials: MA
authors.lastname: Panaro
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005492:Folic Acid / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D005492:Folic Acid; D052247:Nitric Oxide Synthase Type II