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


CONCLUSIONS
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.
Baba
Haruna
H
Department of Pediatrics and Adolescence Medicine, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Ohtsuka
Yoshikazu
Y
Fujii
Tohru
T
Haruna
Hidenori
H
Nagata
Satoru
S
Kobayashi
Hiroyuki
H
Yamataka
Atsuyuki
A
Shimizu
Toshiaki
T
Miyano
Takeshi
T
Yamashiro
Yuichiro
Y
D001656:Biliary Atresia / Q000150:complications / Q000276:immunology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008099:Liver / Q000276:immunology*; D008103:Liver Cirrhosis / Q000276:immunology* / Q000378:metabolism; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D054398:Receptors, CCR4 / Q000096:biosynthesis; D019713:Receptors, CCR5 / Q000096:biosynthesis; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis
D054398:Receptors, CCR4; D019713:Receptors, CCR5; D019714:Tissue Inhibitor of Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9