S100B has a crucial role in inflammation and immune response in the in vivo model of Multiple Sclerosis
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1
Research Institute for Medicines (iMed.ULisboa), Portugal
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2
Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of Lisbon, Portugal
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3
Research Institute for Medicines (iMed.ULisboa), Portugal
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4
Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Portugal
Multiple Sclerosis (MS), an autoimmune and chronic demyelinating disease of the
CNS, cause physical and cognitive disability in young adults. The experimental autoimmune encephalomyelitis (EAE), most common animal model for MS, is based on CD4+/CD8+ T-cell mediated self-reaction against components of myelin. These cells along with microglia recruit other immune cells from the circulating blood, leading to inflammation, gliosis, focal demyelination and neurological affections, major hallmarks of the disease. Interestingly, S100B, a small inflammatory molecule, is increased in the CSF and serum of MS patients. Recently, we directly correlated increased levels of S100B with demyelination and inflammatory processes, using an ex vivo demyelination model, where S100B inhibition by a small molecule showed promising results. Here, we aimed to assay whether S100B targeting with a small molecule in the EAE model could ameliorate MS-like pathogenesis.
EAE was induced in female C57BL/6J wild-type mice and two groups were formed: vehicle group (saline) and EAE-treated group (small molecule, 4mg/kg, i.p., daily). Then, we evaluated clinical score and body weight during 30-days of experiments, immune cell response at the peak of the disease (around 14 days) and CNS pathogenesis at end-point.
Our results demonstrated that disease was delayed in EAE animals following treatment with a small molecule, reaching a lower clinical score and having a faster recovery, which is corroborated by less motor disability. In EAE-induced animals was observed increased percentage of demyelination, which was counteracted upon treatment with a small molecule. Moreover, EAE-treated animals also showed reduction of astrocyte and microglia reactivity, leading to the prevention of the exacerbated expression of inflammatory factors (TNF-α/IL-1β) and increasing that anti-inflammatory ones (IL-10). Furthermore, preliminary data show that, EAE-treated animals have a reduced cell infiltration in lumbar and thoracic regions of the spinal cord. Interestingly, at the peak of the disease EAE-treated animals also showed a decreased percentage of Th1 and Th17 cells alongside with decreased Th17/Treg ratio.
Overall, our results indicate that S100B is involved in MS pathology both with an effect at CNS resident cells as well as at the immune cells, suggesting that its inhibition may be a new therapeutic strategy acting at different mechanisms of MS pathogenesis.
Acknowledgements
.Funded by GMSI-Merck to AF, by FCT UID/DTP/04138/2013 to iMed.ULisboa and post-doctoral grant SFRH/BPD/96794/2013 to AB.
Keywords:
EAE (experimental autoimmune encephalomyelitis),
demyelination,
Glial activation,
Inflammation,
immune response,
Multiple Sclerosis
Conference:
XVI Meeting of the Portuguese Society for Neuroscience (SPN2019), Lisboa, Portugal, 30 May - 1 Jun, 2019.
Presentation Type:
Pitch communication + Poster presentation
Topic:
Glia / Neuroinflammation
Citation:
Barateiro
A,
Barros
C,
Soromenho
B,
Basto
AP,
Freitas
R,
Brites
D,
Graça
L and
Fernandes
A
(2019). S100B has a crucial role in inflammation and immune response in the in vivo model of Multiple Sclerosis.
Front. Cell. Neurosci.
Conference Abstract:
XVI Meeting of the Portuguese Society for Neuroscience (SPN2019).
doi: 10.3389/conf.fncel.2019.01.00052
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Received:
16 Apr 2019;
Published Online:
27 Sep 2019.
*
Correspondence:
Prof. Adelaide Fernandes, Research Institute for Medicines (iMed.ULisboa), Lisboa, Portugal, amaf@ff.ulisboa.pt