Abstract:
BACKGROUND AND AIMS:Surgical management of extrahepatic cholestasis is frequently complicated by bacterial translocation and severe liver injury. The aim of this study was to clarify the involvement of Toll-like receptors (TLRs) in the pathogenesis of bacterial translocation and liver injury in obstructive cholestasis. METHODS:TLR2 deficient (TLR2(-/-)), MyD88(-/-), Jalpha281(-/-), gld/gld, and lpr/lpr mice, all of which have a C57BL/6 background, and C3H/HeN and TLR4 mutated C3H/HeJ mice were subjected to bile duct ligation (BDL). Faecal IgA and serum alanine aminotransferase levels were determined after BDL. Apoptosis was examined by histological and flow cytometric analyses of cells from Peyer's patches and the liver. RESULTS:The size and number of B cells in Peyer's patches markedly decreased on day 3 after BDL. Increased apoptosis in Peyer's patch B cells was evident on day 1 after BDL in control mice but not in lpr/lpr, MyD88(-/-), or C3H/HeJ mice. On the other hand, TLR2 and Fas ligand expression on intrahepatic NK1.1(+) T cells increased on day 1 after BDL in C57BL/6 mice. Liver injury and apoptosis were evident on day 1 after BDL in control and C3H/HeJ mice but were significantly reduced in TLR2(-/-), Jalpha281(-/-), gld/gld, and lpr/lpr mice. CONCLUSIONS:TLR4 and TLR2 may play important roles in Fas dependent apoptosis in Peyer's patch B cells and hepatocytes, respectively, at an early stage after BDL in mice.
journal_name
Gutjournal_title
Gutauthors
Ogawa A,Tagawa T,Nishimura H,Yajima T,Abe T,Arai T,Taniguchi M,Takeda K,Akira S,Nimura Y,Yoshikai Ydoi
10.1136/gut.2005.065318keywords:
subject
Has Abstractpub_date
2006-01-01 00:00:00pages
105-13issue
1eissn
0017-5749issn
1468-3288pii
gut.2005.065318journal_volume
55pub_type
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