title: Anthocyanin effects on microglia M1/M2 phenotype: Consequence on neuronal fractalkine expression.
abstract: Microglia mediate multiple aspects of neuroinflammation, including cytotoxicity, repair, regeneration, and immunosuppression due to their ability to acquire diverse activation states, or phenotypes. Modulation of microglial phenotype or microglia-neuron crosstalk can be an appealing neurotherapeutic strategy. Anthocyanins are a class of flavonoids found e.g., in berries that has been attracting interest due to its neuroprotective potential. However, there are no data clarifying the impact of anthocyanins on microglial phenotype or on microglia-neuron crosstalk (CX3CR1/CX3CL1). N9 microglia cell line was treated with 1μM cyanidin (Cy), cyanidin-3-glucose (Cy3glc) and a methylated form of cyanidin-3-glucose (Met-Cy3glc) in basal conditions and with LPS/IL-4 stimulation. SH-SY5Y cell line was treated with the conditioned medium of microglia and with the anthocyanins alone. At basal conditions, microglia treatment with anthocyanins for 24h induced a less pro-inflammatory profile. Decreased TNF-α mRNA expression was induced either by Cy and Met-Cy3glc. LPS markedly increase IL-6 mRNA expression, which was lowered by Cy3glc. IL-1β LPS-induced expression was reverted by Cy. Cy increased CX3CL1 mRNA expression in SH-SY5Y comparing either with control or LPS. Anthocyanins and metabolites were not able to shift microglia to an M2 strict phenotype however they did interact with microglia biology. There was an attenuation of M1 phenotype and increase of neuronal expression of CX3CL1 mRNA. Understanding how flavonoids modulate microglia-neuron crosstalk can open new directions for future nutritional interventions.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; CINTESIS-Center for Research in Health Technologies and Information Systems, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal.
authors.forename: Manuela
authors.initials: M
authors.lastname: Meireles
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; CINTESIS-Center for Research in Health Technologies and Information Systems, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Marques
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; CINTESIS-Center for Research in Health Technologies and Information Systems, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal.
authors.forename: Sónia
authors.initials: S
authors.lastname: Norberto
authors.affiliation: Life Sciences Department, University of Coimbra, 3001-401 Coimbra, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Santos
authors.affiliation: REQUIMTE/LAQV, Faculty of Sciences, University of Porto, 4169-009 Porto, Portugal.
authors.forename: Iva
authors.initials: I
authors.lastname: Fernandes
authors.affiliation: REQUIMTE/LAQV, Faculty of Sciences, University of Porto, 4169-009 Porto, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Mateus
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; CINTESIS-Center for Research in Health Technologies and Information Systems, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; REQUIMTE/LAQV, Faculty of Sciences, University of Porto, 4169-009 Porto, Portugal; Faculty of Nutrition and Food Sciences, University of Porto, 4200-465 Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Faria
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; CINTESIS-Center for Research in Health Technologies and Information Systems, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal. Electronic address: ccalhau@med.up.pt.
authors.forename: Conceição
authors.initials: C
authors.lastname: Calhau
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D000073883:CX3C Chemokine Receptor 1; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000145:classification / Q000187:drug effects*; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism
chemical_list: D000872:Anthocyanins; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D017077:Culture Media, Conditioned; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D052247:Nitric Oxide Synthase Type II; D005947:Glucose
keywords: Flavonoids; Fractalkine; M1/M2 phenotype; Microglia; Microglia-neuron crosstalk