The role of Heme oxygenase 1 in Systemic Lupus Erithematosus

MACKERN OBERTI, JUAN PABLO; HERRADA, ANDRÉS; CARRENO, LEANDRO; GOMEZ, ROBERTO; ANEGON, IGNACIO; JACOBELLI, SERGIO; LLANOS, CAROLINA; KALERGIS, ALEXIS

Valdivia

Congreso; XXXIV REUNIÓN ANUAL SOCIEDAD DE BIOQUÍMICA Y BIOLOGÍA MOLECULAR DE CHILE; 2011

SOCIEDAD DE BIOQUÍMICA Y BIOLOGÍA MOLECULAR DE CHILE

Heme oxygenase (HO) is an enzyme that catalyzes heme. The HO-1 is an inducible isoform with immunoregulatory functions. HO-1 induction is associated with immune regulation as suppression of Th1- cytokine production. The aim of this work was to study HO-1 levels in Systemic Lupus Erithematosus (SLE) patients and evaluate the beneficial effects of an HO-1 inducer in a mice model of SLE, C57BL/6 FcγRIIb KO. PBMCs were obtained from 20 SLE patients and 10 Healthy controls (HC). Expression of HO-1, MHC class II and CD86 was measured by flow cytometry. 17 weeks old FcγRIIb KO were used (n=9), 5 mice were inoculated with Cobalt-Protoporphyrin (CoPP)(ip) for 6 months. A hallmark of SLE is nephritis, which could be assessed by proteinuria reactive strips. In this study, we show that CD14+ cells from SLE patients expressed less HO-1 than did cells of HC (relative expression, HC = 1.03±0.08 and LES = 0.67±0.04). HO-1 expression was not changed in CD4+ and CD11c+ cells from SLE patients. The expression of MHCII and CD86 on CD14+ cells from SLE patients were similar to HC. When the HO-1 inducer CoPP was chronically administered to FcγRIIb KO mice we observed a diminished incidence (0%) of proteinuria as compared to control mice (50%). Reduced expression of HO-1 in monocytes from SLE patients suggests that HO-1 may be involved in SLE pathology. This notion is supported by the prevention of glomerulonephritis in SLE-prone mice by the induction of HO-1.