| Autor: |
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 |
| Zdroj: |
Journal of Pharmaceutical Investigation; 20240101, Issue: Preprints p1-11, 11p |
| Abstrakt: |
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 the l-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. |
| Databáze: |
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