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Toll-like Receptor mRNA Expression in Liver Tissue From Patients With Biliary Atresia

Saito, Takeshi; Hishiki, Tomoro; Terui, Keita; Mitsunaga, Tetsuya; Terui, Elena; Nakata, Mitsuyuki; Yoshida, Hideo

Journal of Pediatric Gastroenterology & Nutrition: December 2011 - Volume 53 - Issue 6 - p 620–626
doi: 10.1097/MPG.0b013e3182307c9c
Original Articles: Hepatology and Nutrition

Background and Aim: Inappropriate host immunological reactions against unknown ligands via the Toll-like receptor (TLR) cascades may trigger progressive inflammatory biliary destruction that manifests as biliary atresia (BA) in newborns or infants. The aim of the study was to clarify the role of the innate immune system in the development of BA.

Patients and Methods: Liver tissue was obtained from 49 patients with pediatric hepatobiliary diseases: 19 with BA, 21 with choledochal cysts, and 9 with other hepatobiliary diseases. BA samples obtained during the initial portoenterostomy and reoperation or liver transplantation (LT) were classified as early and late BA groups, respectively. Of the early BA group, those requiring LT were designated as the LT group, and the others were designated as the non-LT group. The mRNA expression levels of TLRs 2, 3, 4, 7, and 8 were determined by real-time quantitative reverse transcription-polymerase chain reaction and were compared between groups. The correlation between TLR mRNA expression level and age at sampling was examined for each TLR in the patients with BA.

Results: TLR8 mRNA, encoding the receptor for single-stranded RNA, was significantly higher in the early BA group, compared with non-BA groups (P = 0.008). Within the BA group, mRNA levels of TLRs 2 and 8 were significantly higher in the early group than in the late group (P = 0.02 and 0.006, respectively), despite there being no significant correlation between TLR mRNA expression and age at sampling, except for TLR7 (r = 0.77, P = 0.001). Compared with the non-LT group, the LT group demonstrated significantly higher mRNA expression of TLRs 3 and 7 (P = 0.02 and 0.01, respectively).

Conclusions: Innate immune responses may contribute to the initiation and progression of BA. Severe inflammation characteristic of BA around the time of the first operation may abate postoperatively, but determination of selected TLR mRNA expression levels in the liver at the time of Kasai portoenterostomy may assist in predicting the prognosis of patients with BA.

Department of Pediatric Surgery (E6), Graduate School of Medicine, Chiba University, Chiba, Japan.

Address correspondence and reprint requests to Takeshi Saito, Department of Pediatric Surgery (E6), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8677, Japan (e-mail:

Received 11 January, 2011

Accepted 15 June, 2011

The present study was supported by Grants-in Aid for Scientific Research from the Japan Society for the Promotion of Science (No. 19791307, 21592273).

The authors report no conflicts of interest.

Copyright 2011 by ESPGHAN and NASPGHAN