OBJECTIVE: To explore the therapeutic potential of CD147/HAb18 mAb in the treatment of RA in severe combined immunodeficiency (SCID) mice engrafted with human cartilage and rheumatoid synovium tissue (SCID-HuRAg). METHODS: SCID-HuRAg mice were treated separately with CD147/HAb18 mAb, anti-TNF-alpha mAb or a combination of both. The mice in control group were treated with anti-Japanese encephalitis virus mAb. The volume of engrafts was measured and the number of inflammatory cells and cartilage erosion score were examined. Expression of MMP-2, -3 and -9 was determined by immunohistochemistry. Human inflammatory cytokine levels in mouse sera were assessed using cytometric bead array kit. RESULTS: The volume of engrafts decreased significantly in SCID-HuRAg mice treated separately with anti-CD147 mAb or anti-TNF-alpha mAb, and in the mice treated with anti-CD147 mAb plus anti-TNF-alpha mAb (P < 0.05). Significant reduction was observed in cartilage erosion score in anti-CD147 treatment group and combined treatment group (P < 0.05). Immunohistochemical analysis showed that expression of MMP-2, -3 and -9 was lower in the anti-CD147 treatment group and combined treatment group than in the control mAb group (P < 0.05). Moreover, the level of TNF-alpha, IL-6 and -8 in CD147 mAb group showed a significant decrease compared with that of the control mAb group (P < 0.05). CONCLUSIONS: CD147/HAb18 mAb can reduce cartilage erosion and synovitis by inhibition of the MMPs and reduction of inflammatory cytokines in SCID-HuRAg mice, which suggests that CD147/HAb18 mAb is a promising treatment option for RA patients.
OBJECTIVE: To explore the therapeutic potential of CD147/HAb18 mAb in the treatment of RA in severe combined immunodeficiency (SCID) mice engrafted with humancartilage and rheumatoid synovium tissue (SCID-HuRAg). METHODS:SCID-HuRAgmice were treated separately with CD147/HAb18 mAb, anti-TNF-alpha mAb or a combination of both. The mice in control group were treated with anti-Japanese encephalitis virus mAb. The volume of engrafts was measured and the number of inflammatory cells and cartilage erosion score were examined. Expression of MMP-2, -3 and -9 was determined by immunohistochemistry. Human inflammatory cytokine levels in mouse sera were assessed using cytometric bead array kit. RESULTS: The volume of engrafts decreased significantly in SCID-HuRAgmice treated separately with anti-CD147 mAb or anti-TNF-alpha mAb, and in the mice treated with anti-CD147 mAb plus anti-TNF-alpha mAb (P < 0.05). Significant reduction was observed in cartilage erosion score in anti-CD147 treatment group and combined treatment group (P < 0.05). Immunohistochemical analysis showed that expression of MMP-2, -3 and -9 was lower in the anti-CD147 treatment group and combined treatment group than in the control mAb group (P < 0.05). Moreover, the level of TNF-alpha, IL-6 and -8 in CD147 mAb group showed a significant decrease compared with that of the control mAb group (P < 0.05). CONCLUSIONS:CD147/HAb18 mAb can reduce cartilage erosion and synovitis by inhibition of the MMPs and reduction of inflammatory cytokines in SCID-HuRAgmice, which suggests that CD147/HAb18 mAb is a promising treatment option for RApatients.
Authors: Katina Schinnerling; Carlos Rosas; Lilian Soto; Ranjeny Thomas; Juan Carlos Aguillón Journal: Front Immunol Date: 2019-02-19 Impact factor: 7.561