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Iguratimod Ameliorates the Severity of Secondary Progressive Multiple Sclerosis in Model Mice by Directly Inhibiting IL-6 Production and Th17 Cell Migration via Mitigation of Glial Inflammation
Nagata, S.; Yamasaki, R.; Takase, E.O.; Iida, K.; Watanabe, M.; Masaki, K.; Wijering, M.H.C.; Yamaguchi, H.; Kira, J.-I.; Isobe, N. Iguratimod Ameliorates the Severity of Secondary Progressive Multiple Sclerosis in Model Mice by Directly Inhibiting IL-6 Production and Th17 Cell Migration via Mitigation of Glial Inflammation. Biology2023, 12, 1217.
Nagata, S.; Yamasaki, R.; Takase, E.O.; Iida, K.; Watanabe, M.; Masaki, K.; Wijering, M.H.C.; Yamaguchi, H.; Kira, J.-I.; Isobe, N. Iguratimod Ameliorates the Severity of Secondary Progressive Multiple Sclerosis in Model Mice by Directly Inhibiting IL-6 Production and Th17 Cell Migration via Mitigation of Glial Inflammation. Biology 2023, 12, 1217.
Nagata, S.; Yamasaki, R.; Takase, E.O.; Iida, K.; Watanabe, M.; Masaki, K.; Wijering, M.H.C.; Yamaguchi, H.; Kira, J.-I.; Isobe, N. Iguratimod Ameliorates the Severity of Secondary Progressive Multiple Sclerosis in Model Mice by Directly Inhibiting IL-6 Production and Th17 Cell Migration via Mitigation of Glial Inflammation. Biology2023, 12, 1217.
Nagata, S.; Yamasaki, R.; Takase, E.O.; Iida, K.; Watanabe, M.; Masaki, K.; Wijering, M.H.C.; Yamaguchi, H.; Kira, J.-I.; Isobe, N. Iguratimod Ameliorates the Severity of Secondary Progressive Multiple Sclerosis in Model Mice by Directly Inhibiting IL-6 Production and Th17 Cell Migration via Mitigation of Glial Inflammation. Biology 2023, 12, 1217.
Abstract
We previously reported a novel secondary progressive multiple sclerosis (SPMS) model, progressive experimental autoimmune encephalomyelitis (pEAE), in oligodendroglia-specific Cx47-inducible conditional knockout (Cx47 icKO) mice. Based on our prior study showing the efficacy of iguratimod (IGU), an anti-rheumatic drug, for acute EAE treatment, we aimed to elucidate the effect of IGU on the SPMS animal model. We induced pEAE by immunizing Cx47 icKO mice with myelin oligodendrocyte glycoprotein peptide 35–55. IGU was orally administered from 17 to 50 days postimmunization. We also prepared primary mixed glial cell culture and measured cytokine levels in the culture supernatant after stimulation with designated cytokines (IL-1α, C1q, TNF-α) and lipopolysaccharide. A migration assay was performed to evaluate the effect of IGU on the migration ability of T cells toward mixed glial cell cultures. IGU treatment ameliorated the clinical signs of pEAE, decreased the demyelinated area, and attenuated glial inflammation on immunohistochemical analysis. Additionally, IGU decreased the intrathecal IL-6 level and infiltrating Th17 cells. The migration assay revealed reduced Th17 cell migration and IL-6 levels in the culture supernatant after IGU treatment. Collectively, IGU successfully mitigated the clinical signs of pEAE by suppressing Th17 migration through inhibition of IL-6 production by proinflammatory-activated glial cells.
Biology and Life Sciences, Neuroscience and Neurology
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