Multiple Sclerosis-associated Bacterial Ligand 654

• Published in: Archives of medical research 2022-02, Vol.53 (2), p.157-162
• Main Authors: Brown, Jordan, Everett, Colleen, Barragan, Jose A., Vargas-Medrano, Javier, Gadad, Bharathi S., Nichols, Frank, Cervantes, Jorge L.
• Format: Article
• Language: English
• Subjects: Cytokines; Fingolimod; Fingolimod Hydrochloride - pharmacology; Humans; IFN-β; Interferon-beta - pharmacology; Ligands; Lipid 654; Lipids - pharmacology; Microglia; Multiple Sclerosis - drug therapy
• ISSN: 0188-4409; 1873-5487
• DOI: 10.1016/j.arcmed.2021.11.002

Many endogenous and exogenous risk factors are associated with multiple sclerosis (MS), but recent studies suggest that microbiome-derived ligands, play a role in the disease process. The goal of this study was to characterize the cellular response elicited in human microglia upon treatment with IFN-β and Fingolimod, two first line medications for the management of MS, and determine whether these treatments affect the response of microglial cells to an MS-associated bacterial ligand, Lipid 654. HMC3 human microglial cells were treated with IFN-β or Fingolimod. Cytokine secretion was evaluated using a multiplex system, and microglia polarization was assessed by flow cytometry. We observed that treatment with IFN-β or Fingolimod induced differential secretion of various pro-inflammatory cytokines. Upon cell stimulation with Lipid 654, we observed that IFN-β and Fingolimod decreased the secretion of M1-associated cytokines. Using flow cytometry, we observed that the decrease in inflammatory cytokine secretion was likely due to a containment of M1 phenotype of microglia after stimulation with Lipid 654. Our findings provide new clues of still unknown mechanisms of action of IFN-β and Fingolimod in human microglia, which will prompt new avenues of research on the use of these therapies in the regulation of the inflammatory response in MS.