Expression of toll-like receptors and type 1 interferon specific protein MxA in biliary atresia.
Viral infection and type I interferon have been implicated in the pathogenesis of biliary atresia (BA), but the expression of toll-like receptors (TLRs) that recognize viruses, as well as of type 1 interferon specific signaling molecules are still unknown in BA. Fresh liver tissues were obtained from patients in early and late stage of BA and from patients with choledochal cyst (CC), as well as from normal controls receiving liver resection for benign lesion other than cholestasis or fibrosis. Archived liver tissues from patients with neonatal hepatitis (NH) were obtained for immunohistochemical studies. TLR2, 3, 4, 7 and 9 that recognized Gram-positive bacteria, double-stranded RNA virus, lipopolysaccharide, single-stranded RNA virus and DNA virus, respectively, were studied. Real-time quantitative reverse transcription polymerase chain reaction (QRT-PCR) was used to quantitate TLR, type I interferon specific molecule MxA, interleukin-6 (IL-6) and IL-8 mRNA expression and immunohistochemistry for TLR 7 and MxA protein staining. These results show that there were significantly higher TLR7 and lower TLR3 and TLR9 mRNA expression in early stage of BA than in CC. MxA mRNA expression was also significantly higher in early stage of BA and in CC than in late stage of BA. Immunoreactive TLR7 and MxA staining was higher in early stage of BA than in late stage of BA, NH and CC, which was associated with significantly higher IL-8 mRNA expression in BA than in CC. The results implicate involvement of TLRs, particularly TLR7, and type 1 specific interferon signaling in the pathogenesis of BA, especially in early stage, which is associated with upregulation of inflammatory cytokines IL-8.
Huang
Ying-Hsien
YH
Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center and the Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC.
Chou
Ming-Huei
MH
Du
Yung-Ying
YY
Huang
Chao-Cheng
CC
Wu
Chia-Ling
CL
Chen
Chao-Long
CL
Chuang
Jiin-Haur
JH
D000293:Adolescent; D000328:Adult; D001656:Biliary Atresia / Q000276:immunology / Q000378:metabolism*; D002675:Child, Preschool; D015529:Choledochal Cyst / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D016555:Matched-Pair Analysis; D064547:Myxovirus Resistance Proteins; D016133:Polymerase Chain Reaction / Q000379:methods; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000378:metabolism
D015850:Interleukin-6; D016209:Interleukin-8; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; C495344:TLR3 protein, human; C495371:TLR9 protein, human; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D019204:GTP-Binding Proteins