Effect of 2-amino-2-(2-(4-octylphenyl) ethyl) propane-1,3-diol hydrochloride (FTY 720) on immune liver injury in mice.
OBJECTIVE
To investigate the protective effect against two immune liver injury models in mice by 2-amino-2-(2-(4-octylphenyl) ethyl) propane-1,3-diol hydrochloride and its possible mechanisms in Con A-induced liver damage.


METHODS
Liver tissue or hepatocyte injury was monitored biochemically by measuring alanine aminotransferase (sALT) and aspartate aminotransferase (sAST) activity. Hematoxylin and eosin (HE) staining was used for histopathological examination. To evaluate the role of IFN-gamma and IL-4 in the liver injury, serum levels of IFN-gamma and IL-4 were determined using commercially available ELISA kit at 12 h after Con A challenge. We also determined FTY 720-induced spleen cell apoptosis by flow cytometry analysis or spleen cell proliferation test.


RESULTS
Different doses of FTY 720 treatment dramatically reduced circulating markers of hepatocyte injury in two kinds of immunological liver injury models. FTY 720 dramatically reduced the elevated serum IFN-gamma and IL-4 levels after Con A injection. Effect of spleen cell supernatants treated with Con A or FTY 720 on hepatocytes showed that ALT activities in cultured hepatocyte supernatants in Con A treatment group increased markedly and FTY 720 could reduce this elevated ALT activities in FTY 720 treatment group. FTY 720 dose-dependently increased the percentage of apoptotic cells in T cells and inhibited splenocyte proliferation induced by Con A.


CONCLUSIONS
Pretreatment with FTY 720 was shown to produce protective effect on the immune liver injury in mice. The possible mechanism of FTY 720 on Con A-induced liver damage is that it could inhibit lymphocyte proliferation and induce lymphocyte apoptosis, resulting in the reduction of IL-4 or IFN-gamma release, and subsequently protecting liver from being damaged by Con A.
He
Jing-Hua
JH
Department of Pharmacology, Basic Medical School, Peking University Health Science Center, Beijing 100083, China.
Zhang
Hui-Na
HN
Lin
Zhi-Bin
ZB
D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001219:Aspartate Aminotransferases / Q000097:blood; D002455:Cell Division / Q000276:immunology; D003208:Concanavalin A; D000068876:Fingolimod Hydrochloride; D022781:Hepatocytes / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008070:Lipopolysaccharides; D008107:Liver Diseases / Q000188:drug therapy* / Q000276:immunology*; D008297:Male; D051379:Mice; D009163:Mycobacterium bovis; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013110:Sphingosine / Q000031:analogs & derivatives; D013154:Spleen / Q000166:cytology / Q000276:immunology
D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D011409:Propylene Glycols; D003208:Concanavalin A; D015847:Interleukin-4; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine