Effect of intraperitoneal injection of anti-IL-33 antibody on hepatic fibrosis induced by CCl4 in mice

Abstract

Objective To study the role of IL-33 in the pathogenesis of liver fibrosis. Methods Carbon tetrachloride(CCl4)-induced mouse liver fibrosis model was established in C57BL/6J mice Twenty C57BL/6J mice were randomly divided into control group, model group, antibody blocking group and homologous control group with 5 mice in each group..After intraperitoneal administration of interleukin(IL)-33 antibody, serum biochemistry, enzyme-linked immunosorbent assay(ELISA) and real-time quantitative polymerase chain reaction(qPCR) were used to detect liver fibrosis changes in related indicators. Results Compaired with the control group, the levels of IL-33[(18303.1±580.4)pg/mL vs.(4424.2±566.9)pg/mL, P<0.05], IL-4[(707.2±83.8)pg/mL vs.(50.2±2.1)pg/mL, P<0.05], and IL-13[(665.8±75.7)pg/mL vs.(37.8±7.8)pg/mL, P<0.05] in the liver tissue of the model group were significantly increased, while serum aspartate aminotransferase(AST)[(7503.4±614.2)IU/L vs.(44.2±5.7)IU/L, P<0.05] and alanine aminotransferase (ALT)[(6106.2±465.7)IU/L vs.(44.2±5.7)IU/L, P<0.05] levels were also elevated.The expression of matrix metalloproteinases(MMP)2 [(3.86±0.23)vs.(1.00±0.04), P<0.05] and MMP9 [(3.36±0.19)vs.(1.00±0.04), P<0.05] in the liver tissue of model group mice were significantly elevated and the collagen was significantly deposited[(2704.0±83.3)μg/mL vs.(1425.4±37.0)μg/mL, P<0.05]. After blocking IL-33 with antibodies, IL-4[(707.2±83.8)pg/mL vs.(344.6±51.6)pg/mL, P<0.05 and IL-13 [(665.8±75.7)pg/mL vs.(284.6±65.8)pg/mL, P<0.05] in liver homogenates of model group mice were significantly reduced, and the levels of AST[(7503.4±614.2)IU/L vs.(3883.2±317.0) IU/L, P<0.05] and ALT[(6106.2±465.7)IU/L vs.(3684.4±169.0)IU/L, P<0.05] in serum were significantly decreased compared with control group.The expression of MMP2[(3.86±0.23) vs.(1.94±0.17), P<0.05] and MMP9 [(3.36±0.19)vs.(2.20±0.13), P<0.05] were significantly reduced in the liver tissue of model group mice, and the deposition of collagen was also significantly reduced [(2704.0±83.3)μg/mL vs.(1894.2±174.1)μg/mL, P<0.05]. Conclusion IL-33 is closely related to the pathogenesis of liver fibrosis.Blocking IL-33 may become a new strategy to treat hepatic fibrosis. Key words: Liver fibrosis; Interleukin-33