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Volume 123, Issue 4, Pages (October 2002)

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Presentation on theme: "Volume 123, Issue 4, Pages (October 2002)"— Presentation transcript:

1 Volume 123, Issue 4, Pages 1311-1322 (October 2002)
Cyclooxygenase-2 gene disruption attenuates the severity of acute pancreatitis and pancreatitis-associated lung injury  Richard T. Ethridge, Dai H. Chung, Michele Slogoff, Richard A. Ehlers, Mark R. Hellmich, Srinivasan Rajaraman, Hiroshi Saito, Tatsuo Uchida, B.Mark Evers  Gastroenterology  Volume 123, Issue 4, Pages (October 2002) DOI: /gast Copyright © 2002 American Gastroenterological Association Terms and Conditions

2 Fig. 1 COX-2 protein expression in the pancreas after cerulein-induced pancreatitis. (A) Western blot analysis of pancreata harvested over a time course (0, 1, 16, and 24 hours) after intraperitoneal injections (9 total) of saline (control [CON]) or cerulein (CAE; 50 μg/kg) and probed for COX-2 and COX-1 expression. COX-2 expression was increased with cerulein-induced pancreatitis compared with control (saline-injected); COX-1 levels were not altered. (B) Immunohistochemical analysis of pancreata from saline (CON) and cerulein (CAE)-injected mice harvested 1 hour after the last intraperitoneal injection. Pancreata were fixed in 10% formalin, sectioned, and stained with an ABC staining system using a COX-2 primary antibody. COX-2 expression was increased throughout the pancreatic acini with cerulein-induced pancreatitis. Mean ± SEM. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

3 Fig. 2 Effects of the COX-2 inhibitor (NS-398) on pancreatic inflammatory changes following pancreatitis. (A) Representative H&E-stained sections of pancreas in control (CON) mice not given cerulein, in mice given cerulein (CAE), and in mice given NS-398 (10 mg/kg) at the same time as the first cerulein injections. (B) Histologic sections of pancreata harvested 1 hour after injections of saline (CON), cerulein alone, or NS-398 (1, 5, or 10 mg/kg) given at the same time as the first injection of cerulein were scored from 0 (normal) to 3 (severe) for edema, inflammation, vacuolization, and necrosis as described in Materials and Methods. Mean ± SEM; *P < 0.05 vs. saline-injected controls; †P < 0.05 vs. cerulein alone. This figure shows one experiment testing 5 mice per group. The results were similar in 4 additional experiments. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

4 Fig. 3 Serum PGE2 and amylase levels with pancreatitis. Serum (A) PGE2 and (B) amylase levels in mice injected with saline, cerulein (50 mg/kg; 9 injections) alone, or NS-398 (10 mg/kg) given at the same time as the first injection of cerulein and assessed over a time course (0, 1, 16, and 24 hours) after the last injection. Mean ± SEM; n = 9 mice per group; *P < 0.05 vs. saline treatment; †P < 0.05 vs. cerulein treatment alone. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

5 Fig. 4 Assessment of inflammatory changes of pancreatitis in wild-type, Ptgs2 heterozygote, and Ptgs2-deficient mice. (A) Representative H&E-stained sections of pancreata were examined by light microscopy in Ptgs2 wild-type (+/+), heterozygote (+/−), and knockout (−/−) mice after injections of saline (control [CON]) or cerulein (CAE). (B) Histologic sections of pancreas harvested at 0 hours after cerulein injections in Ptgs2 wild-type (+/+), heterozygote (+/−), and knockout (−/−) mice were scored from 0 (normal) to 3 (severe) for edema, inflammation, vacuolization, and necrosis as described in Materials and Methods. Mean ± SEM; *P < 0.05 vs. wild type (+/+). This figure shows one experiment testing 4–5 mice per group. The results were similar in 4 additional experiments. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

6 Fig. 5 Assessment of inflammatory changes in the lung associated with pancreatitis in Ptgs2 wild-type, heterozygote, and knockout mice. (A) Representative H&E-stained sections of lung were examined by light microscopy in Ptgs2 wild-type (+/+), heterozygote (+/−), and knockout (−/−) mice after injections of saline (control [CON]) or cerulein (CAE). (B) Histologic sections of lung harvested at 1 hour after cerulein injections in Ptgs2 wild-type (+/+), heterozygote (+/−), and knockout (−/−) mice were scored from 0 (normal) to 3 (severe) for edema and inflammation. Mean ± SEM; *P < 0.05 vs. wild type (+/+); †P < 0.05 vs. heterozygote (+/−). This figure shows data for 11–16 mice per group. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

7 Fig. 6 MPO activity. MPO activity was measured in the (A) pancreas and (B) lung in Ptgs2 wild-type (+/+), heterozygote (+/−), and knockout (−/−) mice 0 hours after completion of the cerulein injections and in saline-injected control mice. Data are expressed as MPO activity (U/mg of protein); *P < 0.05 vs. control; †P < 0.05 vs. wild type [+/+]). This figure shows data for 11–14 mice per group. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

8 Fig. 7 Determination of inflammatory changes in the pancreas and lung associated with pancreatitis in wild-type Ptgs1 heterozygote and Ptgs1-deficient mice. (A) Histologic sections of pancreas harvested 1 hour after cerulein injections in Ptgs1 wild-type (+/+), heterozygote (+/−), and knockout (−/−) mice were scored from 0 (normal) to 3 (severe) for edema, inflammation, vacuolization, and necrosis as described in Materials and Methods. Mean ± SEM; *P < 0.05 vs. wild type (+/+); †P < 0.05 vs. heterozygote (+/−). This figure shows data for 9–12 mice per group. (B) Histologic sections of lung harvested 1 hour after cerulein injections in Ptgs1 wild-type (+/+), heterozygote (+/−), and knockout (−/−) mice were scored from 0 (normal) to 3 (severe) for edema and inflammation. Mean ± SEM; *P < 0.05 vs. wild type (+/+). This figure shows data for 13–16 mice per group. (C) MPO activity was measured in the pancreas and lung in Ptgs1 wild-type (+/+), heterozygote (+/−), and knockout (−/−) mice 0 hours after completion of the cerulein injections and in saline-injected control (CON) mice. Data are expressed as MPO activity (U/mg of protein); *P < 0.05 vs. control; †P < 0.05 vs. wild type (+/+). This figure shows data for 11–14 mice per group. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions


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