2004Journal of Pediatric Gastroenterology and NutritionRequires access

P0209 IMMUNOLOGICAL ANALYSIS OF THE LIVER FROM BA PATIENTS

Hideo Baba, Yuuichirou Ohtsuka, Takeshi Fujii, Atsushi Noguchi, Atsushi Unno, Asami Tokita, S. Nagata, Tomohito Shimizu, Y. Yamashiro

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Abstract

Introduction: BA is consisted of bile duct obstruction that is often observed in early infancy. There are several pathogenesis considered in BA, including choledochalpancreaticoductal junction anomaly. Immunological involvements are also suggested after the findings of T cells infiltration with enhanced ICAM-1 expression around the bile ducts in BA patients. Matrix Metalloproteinase(MMP) are secreted by stromal cells under the stimulations of cytokines, such as IFN-ƒÁ and TNF-ƒ¿, secreted from T(Th1)cells. Methods: To investigate the involvement of MMPs in the pathogenesis of BA, the expressions of CCR4, CCR5, MMP3, MMP9 and their inhibitors TIMP1, TIMP2,and TIMP3-mRNA were analyzed by RT-PCR using the liver tissue samples from 5 BA patients. Results: Expression of CCR5 (representing Th1 cells)-mRNA was higher than that of CCR4 (representing Th2 cells)-mRNA in BA patients. MMP3 and MMP9-mRNA were confirmed by PT-PCR. Expression of MMP3-mRNA was relatively higher then that of MMP9-mRNA. TIMP1, TIMP2 and TIMP3-mRNA were also confirmed. The mRNA expression of TIMP1 was relatively higher than those of TIMP2 and TIMP3. Conclusion: MMP is involving in tissue injury and remodeling. Our findings suggest that imbalanced production of MMPs and their inhibitors TIMPs, probably introduced by the immunological reactions, is one of the key mechanisms of pathogenesis and prognosis of BA.

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Introduction: BA is consisted of bile duct obstruction that is often observed in early infancy. There are several pathogenesis considered in BA, including choledochalpancreaticoductal junction anomaly. Immunological involvements are also suggested after the findings of T cells infiltration with enhanced ICAM-1 expression around the bile ducts in BA patients. Matrix Metalloproteinase(MMP) are secreted by stromal cells under the stimulations of cytokines, such as IFN-ƒÁ and TNF-ƒ¿, secreted from T(Th1)cells. Methods: To investigate the involvement of MMPs in the pathogenesis of BA, the expressions of CCR4, CCR5, MMP3, MMP9 and their inhibitors TIMP1, TIMP2,and TIMP3-mRNA were analyzed by RT-PCR using the liver tissue samples from 5 BA patients. Results: Expression of CCR5 (representing Th1 cells)-mRNA was higher than that of CCR4 (representing Th2 cells)-mRNA in BA patients. MMP3 and MMP9-mRNA were confirmed by PT-PCR. Expression of MMP3-mRNA was relatively higher then that of MMP9-mRNA. TIMP1, TIMP2 and TIMP3-mRNA were also confirmed. The mRNA expression of TIMP1 was relatively higher than those of TIMP2 and TIMP3. Conclusion: MMP is involving in tissue injury and remodeling. Our findings suggest that imbalanced production of MMPs and their inhibitors TIMPs, probably introduced by the immunological reactions, is one of the key mechanisms of pathogenesis and prognosis of BA.

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Available abstract

Introduction: BA is consisted of bile duct obstruction that is often observed in early infancy. There are several pathogenesis considered in BA, including choledochalpancreaticoductal junction anomaly. Immunological involvements are also suggested after the findings of T cells infiltration with enhanced ICAM-1 expression around the bile ducts in BA patients. Matrix Metalloproteinase(MMP) are secreted by stromal cells under the stimulations of cytokines, such as IFN-ƒÁ and TNF-ƒ¿, secreted from T(Th1)cells. Methods: To investigate the involvement of MMPs in the pathogenesis of BA, the expressions of CCR4, CCR5, MMP3, MMP9 and their inhibitors TIMP1, TIMP2,and TIMP3-mRNA were analyzed by RT-PCR using the liver tissue samples from 5 BA patients. Results: Expression of CCR5 (representing Th1 cells)-mRNA was higher than that of CCR4 (representing Th2 cells)-mRNA in BA patients. MMP3 and MMP9-mRNA were confirmed by PT-PCR. Expression of MMP3-mRNA was relatively higher then that of MMP9-mRNA. TIMP1, TIMP2 and TIMP3-mRNA were also confirmed. The mRNA expression of TIMP1 was relatively higher than those of TIMP2 and TIMP3. Conclusion: MMP is involving in tissue injury and remodeling. Our findings suggest that imbalanced production of MMPs and their inhibitors TIMPs, probably introduced by the immunological reactions, is one of the key mechanisms of pathogenesis and prognosis of BA.

Key concepts: TIMP1, MMP3, Pathogenesis, Matrix metalloproteinase, MMP9, Messenger RNA, Medicine, Tissue inhibitor of metalloproteinase

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