Immunological investigation of the hepatic tissue from infants with biliary atresia.

PURPOSE: Matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] have been implicated in tissue injury and remodeling in many organs. The objective of this study was to evaluate the expression of MMP-3 and -9, and TIMP-1, -2, and -3 and their relationship to liver fibrosis in infants with biliary atresia.

METHODS

The expression of MMP-3 and-9 and TIMP-1, -2 and -3 was investigated in liver tissue samples of nine patients with biliary atresia. In addition, the expression of CCR-4 and CCR-5 was analyzed to investigate the activation of Th1 and Th2 cells. The mRNA levels were measured by semiquantitative reverse transcriptase polymerase chain reaction.

RESULTS

The expression of MMP-3 was higher than that of MMP-9 in all samples (P < 0.01). The expression of TIMP-1 was higher than that of TIMP-2 and -3 in all samples (P < 0.01). The expression of CCR-5 was higher than that of CCR-4 (P < 0.05), which implied higher activation of Th1 cells relative to Th2 cells.

CONCLUSION

Our findings suggest that MMP-3, possibly induced by Th1 cytokines, and its balance with TIMP-1, may be one of the factors involved in the pathogenesis of biliary atresia.