Galectin-1 exerts immunomodulatory and protective effects on concanavalin A-induced hepatitis in mice.
Galectin-1, an endogenous lectin with immunomodulatory activities, induces selective, Fas-independent apoptosis of activated T cells. The aim of the present study was to evaluate the effect galectin-1 exerts on concanavalin A (Con A)-induced hepatitis, a T-cell-dependent model of liver injury. Con A administration resulted in liver injury, as shown by the increased transaminase plasma levels and liver DNA fragmentation, and caused spleen T-cell activation, which was associated with a strong increment in liver infiltrating T helper cells. Moreover, Con A injection leads to a marked increase in plasma tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) levels. Galectin-1 pretreatment dose-dependently prevented both liver injury and T-helper cell liver infiltration induced by Con A. In vivo and in vitro experiments indicated that the protective effects of galectin-1 depend on the selective elimination of Con A-activated T cells. In addition, galectin-1 almost completely prevented the Con A-induced increase in plasma TNF-alpha and IFN-gamma, an effect that was, at least in part, independent on the elimination of activated T helper cells, because galectin-1 prevented lipopolysaccharide (LPS)-induced release of TNF-alpha and IFN-gamma also from macrophages in vitro, without affecting their viability. The present study suggests that galectin-1 is potentially useful in the treatment of T-cell-mediated human liver disorders.
Santucci
L
L
Clinica di Gastroenterologia ed Epatologia, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Perugia, Perugia, Italy. gastro1@unipg.it
Fiorucci
S
S
Cammilleri
F
F
Servillo
G
G
Federici
B
B
Morelli
A
A
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology* / Q000473:pathology*; D003208:Concanavalin A; D016207:Cytokines / Q000037:antagonists & inhibitors; D053222:Fas Ligand Protein; D037483:Galectin 1; D006388:Hemagglutinins / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism
D000276:Adjuvants, Immunologic; D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D037483:Galectin 1; D006388:Hemagglutinins; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2; D019014:fas Receptor; D003208:Concanavalin A