Objective: To investigate the effects of HS1-associated protein X-1 (HAX-1) on the lupus activity of MRL/lpr lupus-like mice.
Methods: Fifteen MRL/lpr mice were divided into 3 equal groups: Group A, injected with phosphate-buffered saline, Group B, injected intraperitoneally with control virus AdEGFP and Group C, injected intraperitoneally with recombinant AdHAX-1 twice a week for 4 weeks. Peripheral blood samples were collected before the injection, and 2 and 4 weeks after the injection to be detected the white blood cell count, antinuclear antibody (ANA), anti-double strand-DNA antibodies, circulating immune complex (CIC), anti-histone antibodies, and interferon (IFN)-gamma. The level of urine protein was measured, too. Then the mice were killed, a kidney underwent direct immunofluorescence (DIF) to observe the deposition of Immune complexes, and the other kidney underwent periodic acid-Schiff (PAS) staining and pathological examination. MTT method was used to detect the proliferation of the lymphocytes in the spleen. Splenocytes were isolated from the other 15 MRL/lpr mice and then divided into 4 groups: Group, transfected with DMRIE-C without plasmid; Group E, as negative control group; Group F, transfected with blank plasmid pGenesil-1; and Group G, transfected with pGenesil-HAX-1. Forty-eight hours later MTT method was used to detect the proliferation rateof the spleen lymphocytes.
Results: The urine protein level of Group C was significantly higher than those of Groups A and B (both P < 0.01). Four weeks later the levels of ANA, anti-double strand DNA antibodies, and IFN-gamma were all significantly higher than those of Groups A and B (all P < 0.01). Hypercellularity and increased deposition of IgG in glomeruli were also observed in Group C. The score of glomeruli lesion of Group C (1.50 +/- 0.34) was significantly higher than those of Groups A (0.67 +/- 0.14) and Groups B (0.81 +/- 0.26) (both P < 0.01). MTT method showed that the growth curve of the spleen lymphocytes of Group C was higher than those of Groups A and B. The spleen lymphocyte proliferation rate and the levels of IFN-gamma of Group G was significantly lower than that of Group F (both P < 0.05).
Conclusion: One of the important factors in apoptosis regulation of SLE, HAX-1 may be involved in the pathogenesis of SLE, and the silence of HAX-1 may be beneficial for the improvement of SLE.