Genetic induction of proinflammatory immunity in children with biliary atresia

Bezerra, Jorge A.; Tiao, Greg; Ryckman, Frederick C.; Alonso, Marı́a Pilar; Sabla, Gregg; Shneider, Benjamin L.; Sokol, Ronald J.; Aronow, Bruce J.

doi:10.1016/s0140-6736(02)11603-5

Cited by 184 publications

(177 citation statements)

References 30 publications

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“…Bezerra et al showed a 4.6-fold change in hepatic MMP-7 in patients with biliary atresia comparing to those with neonatal intrahepatic cholestasis by cRNA hybridization against oligonucleotide-based gene chips. 24 Chen et al 25 demonstrated a similar result that MMP-7 expression in biliary atresia liver had 2.46-fold change over that in normal liver and 1.93-fold change over diseased controls by cDNA microarray. Notably, MMP-7 was the only MMP significantly upregulated in the liver of biliary atresia in these two studies.…”

Section: Discussionmentioning

confidence: 85%

“…[15][16][17][18][19][20][21][22] To address the major MMPs that involve in the progress of liver fibrosis in biliary atresia, we studied MMP-2, MMP-9 and MMP-13 that were most commonly reported MMPs related to the regulation of liver fibrogenesis. We also studied MMP-7, which has been mentioned being the key regulator of pulmonary fibrosis 23 and is expressed in significantly higher level in DNA microarray 24,25 but not being studied otherwise in liver fibrosis associated with biliary atresia. Real-time quantitative reverse transcriptase-PCR (qRT-PCR) showed a significantly higher expression of MMP-2 and MMP-7 in the late cirrhotic stage of liver compared to the control.…”

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confidence: 99%

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Matrilysin (MMP-7) is a major matrix metalloproteinase upregulated in biliary atresia-associated liver fibrosis

et al. 2005

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Matrix metalloproteinases (MMPs) are the proteases responsible for tissue remodeling during liver fibrosis caused by various disorders including biliary atresia. However, information regarding the relative contribution of these proteases to liver fibrosis is still limited. We studied matrix metalloproteinase-2 (MMP-2), -7, -9 and -13 mRNA expressions in the liver tissue of early-stage biliary atresia at the time of Kasai's procedure, late-stage biliary atresia at the time of liver transplantation with advanced fibrosis and nondiseased control without liver fibrosis. The results of real-time quantitative reverse transcriptase-PCR analysis revealed that only MMP-2 and -7 expressions were significantly different between groups. MMP-2 was significantly higher in Liver Transplantation group than both in Control (P ¼ 0.010) and in Kasai's Procedure (P ¼ 0.001) groups, whereas the difference of MMP-2 expression between Control and Kasai's Procedure was not significant. However, the relative expression level of MMP-7 was sequentially elevated when comparing Control, Kasai's Procedure and Liver Transplantation groups, and there was significant (P ¼ 0.019) difference when comparing Control and Liver Transplantation groups. Moreover, the fold difference in MMP-7 mRNA was much higher than that in MMP-2 mRNA between groups. The expressions of MMP-7 were further confirmed by agarose gel electrophoresis and Western blotting. Immunohistochemical analysis revealed a significant positive correlation of the scores of MMP-7 immunostaining with the stages of liver fibrosis. In situ hybridization demonstrated that the bile ductular epithelial cells, Kupffer cells and hepatocytes were the major producers of matrix metalloproteinase-7 in the liver. Our results imply that MMP-7 is a major MMP associated with the tissue remodeling during the progression of liver fibrosis in biliary atresia. Modern Pathology (2005) 18, 941-950.

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Section: Discussionmentioning

confidence: 85%

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confidence: 99%

Matrilysin (MMP-7) is a major matrix metalloproteinase upregulated in biliary atresia-associated liver fibrosis

et al. 2005

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“…19 There has been some clinical and experimental evidence that BA exhibits a polarized, specifically Th1 immune response, at least in the early stages of the disease (i.e., up to the time of KP). 16,20,21,22 For instance, Mack et al 16 using immunocytochemistry and RT-PCR showed a CD4ϩ and CD8ϩ T cell infiltrate within portal tracts with a localized increased expression of the cytokines IL-2, IFN␥, TNF␣ and IL-12 (but not IL-4 or IL-5). Experimentally (using a rotavirus-induced murine BA model) the same group 20 has shown significant increases in CD4ϩ T cells producing IFN␥ (i.e., Th1 response) with a later influx of activated macrophages producing TNF␣.…”

Section: Discussionmentioning

confidence: 99%

Serial circulating markers of inflammation in biliary atresia—Evolution of the post-operative inflammatory process

et al. 2007

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Biliary atresia (BA) may be characterized as an occlusive cholangiopathy affecting both intraand extra-hepatic parts of the biliary tree, together with a pronounced inflammatory response consisting of hepatic infiltration of (predominantly) CD4؉ lymphocytes and macrophages. Soluble cellular adhesion molecules are also known to be raised at the time of portoenterostomy, presumably reflecting intrahepatic disease. We investigated this measur-

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“…Even if lower in number, neonatal T cells can activate a broad pro-inflammatory program in response to tissue infection, as demonstrated by the effective clearance of RRV from the liver and biliary tract by neonatal CD8+ cells (16). A prominent pro-inflammatory footprint and an enriched population of CD4+ and CD8+ lymphocytes have been reported in the murine model, with evidence of an antigenic oligoclonal expansion (17)(18)(19)(20). The loss of interferon-gamma (IFN-γ) or CD8+ lymphocytes prevents obstruction of bile ducts, suppressing the disease phenotype, and, when virus-primed T cells are transferred to RRV-naive recipients, they home to bile ducts and induce cholangitis.…”

Section: Environmental Triggersmentioning

confidence: 99%