4-Ethylguaiacol modulates neuroinflammation and Th1/Th17 differentiation to ameliorate disease severity in experimental autoimmune encephalomyelitis

dc.contributor.authorWeng, Wen-Tsan
dc.contributor.authorKuo, Ping-Chang
dc.contributor.authorBrown, Dennis A.
dc.contributor.authorScofield, Barbara A.
dc.contributor.authorFurnas, Destin
dc.contributor.authorParaiso, Hallel C.
dc.contributor.authorWang, Pei-Yu
dc.contributor.authorYu, I-Chen
dc.contributor.authorYen, Jui-Hung
dc.contributor.departmentAnatomy and Cell Biology, School of Medicineen_US
dc.date.accessioned2022-10-20T15:32:55Z
dc.date.available2022-10-20T15:32:55Z
dc.date.issued2021-05-11
dc.description.abstractBackground: Multiple sclerosis (MS) is a progressive autoimmune disease characterized by the accumulation of pathogenic inflammatory immune cells in the central nervous system (CNS) that subsequently causes focal inflammation, demyelination, axonal injury, and neuronal damage. Experimental autoimmune encephalomyelitis (EAE) is a well-established murine model that mimics the key features of MS. Presently, the dietary consumption of foods rich in phenols has been reported to offer numerous health benefits, including anti-inflammatory activity. One such compound, 4-ethylguaiacol (4-EG), found in various foods, is known to attenuate inflammatory immune responses. However, whether 4-EG exerts anti-inflammatory effects on modulating the CNS inflammatory immune responses remains unknown. Thus, in this study, we assessed the therapeutic effect of 4-EG in EAE using both chronic and relapsing-remitting animal models and investigated the immunomodulatory effects of 4-EG on neuroinflammation and Th1/Th17 differentiation in EAE. Methods: Chronic C57BL/6 EAE and relapsing-remitting SJL/J EAE were induced followed by 4-EG treatment. The effects of 4-EG on disease progression, peripheral Th1/Th17 differentiation, CNS Th1/Th17 infiltration, microglia (MG) activation, and blood-brain barrier (BBB) disruption in EAE were evaluated. In addition, the expression of MMP9, MMP3, HO-1, and Nrf2 was assessed in the CNS of C57BL/6 EAE mice. Results: Our results showed that 4-EG not only ameliorated disease severity in C57BL/6 chronic EAE but also mitigated disease progression in SJL/J relapsing-remitting EAE. Further investigations of the cellular and molecular mechanisms revealed that 4-EG suppressed MG activation, mitigated BBB disruption, repressed MMP3/MMP9 production, and inhibited Th1 and Th17 infiltration in the CNS of EAE. Furthermore, 4-EG suppressed Th1 and Th17 differentiation in the periphery of EAE and in vitro Th1 and Th17 cultures. Finally, we found 4-EG induced HO-1 expression in the CNS of EAE in vivo as well as in MG, BV2 cells, and macrophages in vitro. Conclusions: Our work demonstrates that 4-EG confers protection against autoimmune disease EAE through modulating neuroinflammation and inhibiting Th1 and Th17 differentiation, suggesting 4-EG, a natural compound, could be potentially developed as a therapeutic agent for the treatment of MS/EAE.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationWeng WT, Kuo PC, Brown DA, et al. 4-Ethylguaiacol modulates neuroinflammation and Th1/Th17 differentiation to ameliorate disease severity in experimental autoimmune encephalomyelitis. J Neuroinflammation. 2021;18(1):110. Published 2021 May 11. doi:10.1186/s12974-021-02143-wen_US
dc.identifier.urihttps://hdl.handle.net/1805/30379
dc.language.isoen_USen_US
dc.publisherBMCen_US
dc.relation.isversionof10.1186/s12974-021-02143-wen_US
dc.relation.journalJournal of Neuroinflammationen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.sourcePMCen_US
dc.subjectMicrogliaen_US
dc.subjectNeuroinflammationen_US
dc.subjectBlood-brain barrieren_US
dc.title4-Ethylguaiacol modulates neuroinflammation and Th1/Th17 differentiation to ameliorate disease severity in experimental autoimmune encephalomyelitisen_US
dc.typeArticleen_US
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