Rahaman, Khandoker Asiqur Hasan, Mahbub Seo, Ji-Eun Muresan, Anca Raluca Song, Hye Jin Min, Hophil Son, Junghyun Lee, Jaeick Lee, Joonhee Kim, Byungjoo Kwon, Oh-Seung 2024-01-19T16:34:40Z 2024-01-19T16:34:40Z 2021-09-02 2020-09 2093-5552 https://pubs.kist.re.kr/handle/201004/118190 Purpose Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease of the dynamic immune system acting against the myelin sheath of neuronal axons in the abluminal (brain-facing) side of the central nervous system. This immune system is greatly influenced by the free amino acid environment from the luminal (blood-facing) side. Whether the luminal and abluminal free amino acid balance influences EAE disease progression is still unclear. Methods Changes in free amino acid levels on both sides of the blood-brain barrier were observed with or without blocking of thel-amino acid transporter (LAT-1) during EAE disease progression. Brain tissue, plasma, splenocytes samples were used to measure free amino acid by LC-MS/MS. Samples were also used to measure cytokines by ELISA and numbers of immune cells by flow cytometry. Results In the chronic stage of EAE progression, clinical scores of LAT-1-inhibited EAE mice were higher than those of normal EAE mice. Significantly elevated T-cell counts, MMP-9 activity, and IL-6 levels were found in the LAT-1-inhibited EAE group. Inhibition of LAT-1 with 2-amino-2-norbornanecarboxylic acid (BCH) treatment resulted in decreased leucine concentration in splenocytes and increased leucine levels in plasma. The leucine levels on the abluminal side of LAT-1-inhibited EAE mice were also significantly higher than those of control mice but not those of EAE mice. Conclusion The increased leucine concentration present at the luminal side crossed the blood brain barrier (BBB) and fueled inflammation with concurrent disease severity in the abluminal side of EAE mice. English 한국약제학회 Severity of the autoimmune encephalomyelitis symptoms in mouse model by inhibition of LAT-1 transporters Article 10.1007/s40005-019-00468-6 1 Journal of Pharmaceutical Investigation, v.50, no.5, pp.481 - 491 Journal of Pharmaceutical Investigation 50 5 481 491 N scopus kci ART002625895 000563801100004 2-s2.0-85076320558 Pharmacology & Pharmacy Pharmacology & Pharmacy Article T Cells Experimental autoimmune encephalomyelitis BCH LAT-1 transporter Leucine