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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2015.11
- 수록면
- 998 - 1,006 (9page)
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Retinols are metabolized into retinoic acids by alcohol dehydrogenase (ADH) and retinaldehyde dehydrogenase (Raldh). However, their roles have yet to be clarified in hepatitis despite enriched retinols in hepatic stellate cells (HSCs). Therefore, we investigated the effects of retinols on Concanavalin A (Con A)-mediated hepatitis. 1 Con A was injected into wild type (WT), Raldh1 knockout (Raldh1-/-), CCL2-/- and CCR2-/- mice. For migration study of regulatory T cells (Tregs), we used in vivo and ex vivo adoptive transfer systems. Blockade of retinol metabolism in mice given 4-methylpyrazole, an inhibitor of ADH, and ablated Raldh1 gene manifested increased migration of Tregs, eventually protected against Con Amediated hepatitis by decreasing interferon-γ in T cells.
Moreover, interferon-γ treatment increased the expression of ADH3 and Raldh1, but it suppressed that of CCL2 and IL-6 in HSCs. However, the expression of CCL2 and IL-6 was inversely increased upon the pharmacologic or genetic ablation of ADH3 and Raldh1 in HSCs. Indeed, IL- 6 treatment increased CCR2 expression of Tregs. In migration assay, ablated CCR2 in Tregs showed reduced migration to HSCs. In adoptive transfer of Tregs in vivo and ex vivo, Raldh1-deficient mice showed more increased migration of Tregs than WT mice. Furthermore,inhibited retinol metabolism increased survival rate (75%) compared with that of the controls (25%) in Con Ainduced hepatitis.
These results suggest that blockade of retinol metabolism protects against acute liver injury by increased Treg migration, and it may represent a novel therapeutic strategy to control T cell-mediated acute hepatitis.
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참고문헌 (40)
참고문헌 신청
Ajuebor, M. N. / 2003 / CC chemokine ligand 2/monocyte chemoattractant protein-1directly inhibits NKT cell IL-4 production and is hepatoprotective in T cell-mediated hepatitis in the mouse / J. Immunol 170:5252~5259
Austenaa, L. M. / 2009 / Retinoic acid dampens LPS-induced NFkappaB activity : results from human monoblasts and in vivo imaging of NF-kappaB reporter mice / J. Nutr. Biochem 20:726~734
Bruhl, H. / 2004 / Dual role of CCR2 during initiation and progression of collagen-induced arthritis : evidence for regulatory activity of CCR2+ T cells / J. Immunol 172:890~898
Choi, Y. S. / 2014 / Liver injury in acute hepatitis A is associated with decreased frequency of regulatory T cells caused by Fas-mediated apoptosis / Gut 64:1303~1313
Chou, H. S. / 2011 / Hepatic stellate cells regulate immune response by way of induction of myeloid suppressor cells in mice / Hepatology 53:1007~1019
Austenaa, L. M. / 2009 / Retinoic acid dampens LPS-induced NFkappaB activity : results from human monoblasts and in vivo imaging of NF-kappaB reporter mice / J. Nutr. Biochem 20:726~734
Bruhl, H. / 2004 / Dual role of CCR2 during initiation and progression of collagen-induced arthritis : evidence for regulatory activity of CCR2+ T cells / J. Immunol 172:890~898
Choi, Y. S. / 2014 / Liver injury in acute hepatitis A is associated with decreased frequency of regulatory T cells caused by Fas-mediated apoptosis / Gut 64:1303~1313
Chou, H. S. / 2011 / Hepatic stellate cells regulate immune response by way of induction of myeloid suppressor cells in mice / Hepatology 53:1007~1019
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