AIM: To investigate the potential role of nuclear factor kappa-B (NF-κB) activation on the reactive oxygen species in rat acute necrotizing pancreatitis (ANP) and to assess the effect of pyrrolidine dithiocarbam...AIM: To investigate the potential role of nuclear factor kappa-B (NF-κB) activation on the reactive oxygen species in rat acute necrotizing pancreatitis (ANP) and to assess the effect of pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB).METHODS: Rat ANP model was established by retrograde injection of 5% sodium taurocholate into biliopancreatic duct. Rats were randomly assigned to three groups (10 rats each): Control group, ANP group and PDTC group. At the 6^th of the model, the changes of the serum amylase,nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD) and pancreatic morphological damage were observed. The expressions of inducible nitric oxide (iNOS) were observed by SP immunohistochemistry. And bhe expressions of NF-κB p65 subunit mRNA were observed by hybridization in situ.RESULTS: Serum amylase and NO level decreased significantly in ANP group as compared with PDTC administrated group [(7 170.40+1 308.63) U/L vs(4 074.10+1 719.78) U/L,P〈0.05], [(76.95±9.04) μmol/L vs (65.18±9.02) μmol/L,P〈0.05] respectively. MDA in both ANP and PDTC group rose significantly over that in control group [(9.88+1.52)nmol/L, (8.60±1.41) nmol/L, vs (6.04:hl.78) nmol/L,P〈0.05], while there was no significant difference between them. SOD levels in both ANP and PDTC group underwent a significant decrease as compared with that in control[(3 214.59±297.74) NU/mL, (3 260.62±229.44) NU/mL,vs(3 977.80+309.09) NU/mL, P〈0.05], but there was no significant difference between them. Though they were still higher bhan those in Control group, pancreas destruction was slighter in PDTC group, iNOS expression and NF-κB p65 subunit mRNA expression were lower in PDTC group as compared with ANP group.CONCLUSION: We conclude that correlation among NF-κB activation, serum amylase, reactive oxygen species level and tissue damage suggests a key role of NF-κB in the pathogenesis of ANP. Inhibition of NF-κB activation may reverse the pancreatic damage of rat ANP and the production of reactive oxygen species.展开更多
AIM:To investigate the mechanisms involved in a possible modulator role of interleukin(IL) -6 signalling on CYR61-CTGF-NOV(CCN) 2/connective tissue growth factor(CTGF) expression in hepatocytes(PC) and to look for a r...AIM:To investigate the mechanisms involved in a possible modulator role of interleukin(IL) -6 signalling on CYR61-CTGF-NOV(CCN) 2/connective tissue growth factor(CTGF) expression in hepatocytes(PC) and to look for a relation between serum concentrations of these two parameters in patients with acute inflammation. METHODS:Expression of CCN2/CTGF,p-STAT3,p-Smad 3/1 and p-Smad2 was examined in primary freshly isolated rat or cryo-preserved human PC exposed to various stimuli by Western blotting,electrophoretic mobility shift assay(EMSA) ,reporter-gene-assays and reversetranscriptase polymerase chain reaction. RESULTS:IL-6 strongly down-regulated CCN2/CTGF protein and mRNA expression in PC,enhanceable by extracellular presence of the soluble IL-6 receptor gp80,and supported by an inverse relation between IL-6 and CCN2/CTGF concentrations in patients'sera.The inhi-bition of TGFβ1 driven CCN2/CTGF expression by IL-6 did not involve a modulation of Smad2(and Smad1/3) signalling.However,the STAT3 SH2 domain binding peptide,a selective inhibitor of STAT3 DNA binding activity,counteracted the inhibitory effect of IL-6 on CCN2/CTGF expression much more pronounced than pyrrolidine-dithiocarbamate,an inhibitor primarily of STAT3 phosphorylation.An EMSA confirmed STAT3 binding to the proposed proximal STAT binding site in the CCN2/CTGF promoter. CONCLUSION:CCN2/CTGF is identified as a hepatocellular negative acute phase protein which is downregulated by IL-6 via the STAT3 pathway through interaction on the DNA binding level.展开更多
Postherpetic neuralgia(PHN) is a severe sequela of herpes zoster(HZ).Until now,only age and pain severity were considered predisposing factors for the development of PHN.We evaluated 49 patients with acute phase HZ,10...Postherpetic neuralgia(PHN) is a severe sequela of herpes zoster(HZ).Until now,only age and pain severity were considered predisposing factors for the development of PHN.We evaluated 49 patients with acute phase HZ,10 of whom developed PHN(Group A) and 39 of whom did not develop PHN(Group B).Twenty-five healthy volunteers similar in age and gender distribution to the study group were recruited as controls(Group C).Numbers of serum CD3+(pan-T lymphocytes),CD4+(helper/inducer),and CD8+(suppressor/cytotoxic) lymphocytes were decreased significantly in Groups A and B relative to the control group,but there were no statistical differences between Groups A and B.Interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-α,IL-8,and IL-10 were significantly elevated in Groups A and B relative to Group C.IL-6 was significantly higher in Group A than in Group B,and was significantly positively correlated with pain severity scored on a visual analog scale.Therefore,we suggest that the inflammatory response,especially that of IL-6,in the acute phase of HZ may be associated with hyperalgesia and the development of PHN.展开更多
文摘AIM: To investigate the potential role of nuclear factor kappa-B (NF-κB) activation on the reactive oxygen species in rat acute necrotizing pancreatitis (ANP) and to assess the effect of pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB).METHODS: Rat ANP model was established by retrograde injection of 5% sodium taurocholate into biliopancreatic duct. Rats were randomly assigned to three groups (10 rats each): Control group, ANP group and PDTC group. At the 6^th of the model, the changes of the serum amylase,nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD) and pancreatic morphological damage were observed. The expressions of inducible nitric oxide (iNOS) were observed by SP immunohistochemistry. And bhe expressions of NF-κB p65 subunit mRNA were observed by hybridization in situ.RESULTS: Serum amylase and NO level decreased significantly in ANP group as compared with PDTC administrated group [(7 170.40+1 308.63) U/L vs(4 074.10+1 719.78) U/L,P〈0.05], [(76.95±9.04) μmol/L vs (65.18±9.02) μmol/L,P〈0.05] respectively. MDA in both ANP and PDTC group rose significantly over that in control group [(9.88+1.52)nmol/L, (8.60±1.41) nmol/L, vs (6.04:hl.78) nmol/L,P〈0.05], while there was no significant difference between them. SOD levels in both ANP and PDTC group underwent a significant decrease as compared with that in control[(3 214.59±297.74) NU/mL, (3 260.62±229.44) NU/mL,vs(3 977.80+309.09) NU/mL, P〈0.05], but there was no significant difference between them. Though they were still higher bhan those in Control group, pancreas destruction was slighter in PDTC group, iNOS expression and NF-κB p65 subunit mRNA expression were lower in PDTC group as compared with ANP group.CONCLUSION: We conclude that correlation among NF-κB activation, serum amylase, reactive oxygen species level and tissue damage suggests a key role of NF-κB in the pathogenesis of ANP. Inhibition of NF-κB activation may reverse the pancreatic damage of rat ANP and the production of reactive oxygen species.
文摘AIM:To investigate the mechanisms involved in a possible modulator role of interleukin(IL) -6 signalling on CYR61-CTGF-NOV(CCN) 2/connective tissue growth factor(CTGF) expression in hepatocytes(PC) and to look for a relation between serum concentrations of these two parameters in patients with acute inflammation. METHODS:Expression of CCN2/CTGF,p-STAT3,p-Smad 3/1 and p-Smad2 was examined in primary freshly isolated rat or cryo-preserved human PC exposed to various stimuli by Western blotting,electrophoretic mobility shift assay(EMSA) ,reporter-gene-assays and reversetranscriptase polymerase chain reaction. RESULTS:IL-6 strongly down-regulated CCN2/CTGF protein and mRNA expression in PC,enhanceable by extracellular presence of the soluble IL-6 receptor gp80,and supported by an inverse relation between IL-6 and CCN2/CTGF concentrations in patients'sera.The inhi-bition of TGFβ1 driven CCN2/CTGF expression by IL-6 did not involve a modulation of Smad2(and Smad1/3) signalling.However,the STAT3 SH2 domain binding peptide,a selective inhibitor of STAT3 DNA binding activity,counteracted the inhibitory effect of IL-6 on CCN2/CTGF expression much more pronounced than pyrrolidine-dithiocarbamate,an inhibitor primarily of STAT3 phosphorylation.An EMSA confirmed STAT3 binding to the proposed proximal STAT binding site in the CCN2/CTGF promoter. CONCLUSION:CCN2/CTGF is identified as a hepatocellular negative acute phase protein which is downregulated by IL-6 via the STAT3 pathway through interaction on the DNA binding level.
基金Project (No.2008ZYC07) supported by the Zhejiang Medical Bureau of China
文摘Postherpetic neuralgia(PHN) is a severe sequela of herpes zoster(HZ).Until now,only age and pain severity were considered predisposing factors for the development of PHN.We evaluated 49 patients with acute phase HZ,10 of whom developed PHN(Group A) and 39 of whom did not develop PHN(Group B).Twenty-five healthy volunteers similar in age and gender distribution to the study group were recruited as controls(Group C).Numbers of serum CD3+(pan-T lymphocytes),CD4+(helper/inducer),and CD8+(suppressor/cytotoxic) lymphocytes were decreased significantly in Groups A and B relative to the control group,but there were no statistical differences between Groups A and B.Interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-α,IL-8,and IL-10 were significantly elevated in Groups A and B relative to Group C.IL-6 was significantly higher in Group A than in Group B,and was significantly positively correlated with pain severity scored on a visual analog scale.Therefore,we suggest that the inflammatory response,especially that of IL-6,in the acute phase of HZ may be associated with hyperalgesia and the development of PHN.