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Blockade of high mobility group box-1 protein attenuates experimental severe acute pancreatitis

World Journal of Gastroenterology 2006年第47期12卷 7666-7670页

作者： Hidehiro Sawa Takashi Ueda Yoshifumi Takeyama Takeo Yasuda Makoto Shinzeki Takahiro Nakajima Yoshikazu Kuroda Department of Gastroenterological Surgery Kobe University Graduate School of Medical Sciences Kobe 650-0017 Japan Department of Surgery Kinki University School of Medicine Osaka-sayama 589-8511 Japan

AIM： To examine the effects of anti-high mobility group box 1 （HIGB1） neutralizing antibody in experimental severe acute pancreatitis （SAP）. METHODS： SAP was induced by creating closed duodenal loop inC3H/HeN mice. SAP was induced immediately after intrapedtoneal injection of anti-HMGB1 neutralizing antibody （200 pg）. Sevedty of pancreatitis, organ injury （liver, kidney and lung）, and bacterial translocation to pancreas was examined 12 h after induction of SAP. RESUlTS： Anti-HHGB1 neutralizing antibody significantly improved the elevation of the serum amylase level and the histological alterations of pancreas and lung in SAR Anti-HHGB1 antibody also significantly ameliorated the elevations of serum alanine aminotransferase and creatinine in SAR However, anti-HHGB1 antibody worsened the bacterial translocation to pancreas. CONClUSION： Blockade of HHGB1 attenuated the development of SAP and associated organ dysfunction, suggesting that HHGB1 may act as a key mediator for inflammatory response and organ injury in SAR

关键词： Severe acute pancreatitis high mobility group box-l Neutralizing antibody Inflammatory response Organ dysfunction Bacterial translocation

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Effects of HMGB1 Expression Suppressed by siRNA on Cell Cycle and Proliferation of Human Cervical Cancer Cell line Hela

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Clinical oncology and cancer researeh 2010年第2期7卷 128-133页

作者： Yuan-yuan QIU Hui-yu WANG Quan HAO Key laboratory of Cancer Prevention and Therapy Tianjin Department of Gynecology Cancer Institute and Hospital of Tianjin Medical University Tianjin 300060 China.

OBJECTIVE In this study, RNA interference was used to evaluate the effects of HMGB1 expression on cell cycle and proliferation of the human cervical cancer cell line *** We had previously constructed and screened effective eukaryotic expression vectors carrying PGCsi3.0-1/ HMGB1 siRNA and PGCsi3.0-3/HMGB1 siRNA, then the vectors were transfected into Hela cells. The expression of HMGB1 before and after transfection in Hela cells were detected by RT-PCR and Western blot. The cell viability and proliferating activity was tested by Trypan blue dye test and MTT, and the cell cycle was determined bv flow *** The introduction of PGCsi3.0-1/HMGB1 siRNA and PGCsi3.0-3/HMGB1 siRNA inhibited the expression of HMGB1 mRNA and protein efficiently and specifically, there was a significant difference between the siRNA groups and the control groups （P 〈 0.05）. The proliferation speed of PGCsi3.0-1 group and PGC si3.0-3 group were obviously slower than those of PGCsi3.0- Neg group and non-transfected group. Flow cytometry showed that the content of DNA in G2 phase in PGCsi3.0-1 group and PGCsi3.0-3 group were obviously more than those in PGCsi3.0- Neg group and non-transfected group, but the content in S phase was less （P 〈 0.01）. The progression of cell cycle was arrested from G2 to S *** PGCsi3.0-1/HMGB1 siRNA and PGCsi3.0-3 /HMGB1 siRNA could specially suppress the expression of HMGB1 gene, inhibit the proliferation speed of Hela cells effectively, and arrest the progression of cell cycle from G2 to S phase. RNAi provides a new approach to the bio-therapy of cervical cancer.

关键词： high mobility group box-l Hela cells RNAinterference cell proliferation cell cycle.

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