AIM: To study the anti-inflammatory effects of cholecystokinin-octapeptide (CCK-8) on lipopolysaccharide (LPS)-induced endotoxic shock (ES) and further investigate its signal transduction pathways involving p38 mitogen-activated protein kinase (MAPK) and IkappaB-alpha. METHODS: Eighty-four rats were divided randomly into four groups: LPS (8 mg.kg(-1), iv) induced ES; CCK-8 (40 microg.kg(-1), iv) pretreatment 10 min before LPS (8 mg.kg(-1)); CCK-8 (40 microg.kg(-1), iv) or normal saline (control) groups. The inflammatory changes of lung and spleen, phagocytic function of alveolar macrophage, quantification of inflammatory cells in bronchoalveolar lavage (BAL) were investigated in rats by using hematoxylin and eosin (HE) staining, phagocytosis of Candida albicans and differential cell counting. Nitric oxide (NO) production in serum, lung and spleen was measured with the Griess reaction. The mechanism involving p38 MAPK and IkappaB-alpha signal pathways was investigated by Western blot. RESULTS: Inflammatory changes of lung and spleen induced by LPS were alleviated by CCK-8, the increase of NO induced by LPS in serum, lung and spleen was significantly inhibited and the neutrophil infiltration in BAL was significantly reduced by CCK-8. The number of neutrophils was (52+/-10)X10(6) cells. (-1) in LPS group, while it decreased to (18+/-4)X10(6) cells. (-1) in CCK-8+LPS (P<0.01). The phagocytic rate of CCK-8 group increased to (62.49+/-9.49) %, compared with control group (48.16+/-14.20) %, P<0.05. The phagocytosis rate was (85.14+/-4.64) % in LPS group, which reduced to (59.33+/-3.14) % in CCK-8+LPS group (P<0.01). The results of phagocytosis indexes showed similar changes. CCK-8 may play an important role in increasing the expression of p38 MAPK and decreasing the degradation of IkappaB-alpha in lung and spleen of ES rats. CONCLUSION: CCK-8 can result in anti-inflammatory effects, which may be related to activation of p38 MAPK and inhibition on the degradation of IkappaB-alpha.
AIM: To study the anti-inflammatory effects of cholecystokinin-octapeptide (CCK-8) on lipopolysaccharide (LPS)-induced endotoxic shock (ES) and further investigate its signal transduction pathways involving p38 mitogen-activated protein kinase (MAPK) and IkappaB-alpha. METHODS: Eighty-four rats were divided randomly into four groups: LPS (8 mg.kg(-1), iv) induced ES; CCK-8 (40 microg.kg(-1), iv) pretreatment 10 min before LPS (8 mg.kg(-1)); CCK-8 (40 microg.kg(-1), iv) or normal saline (control) groups. The inflammatory changes of lung and spleen, phagocytic function of alveolar macrophage, quantification of inflammatory cells in bronchoalveolar lavage (BAL) were investigated in rats by using hematoxylin and eosin (HE) staining, phagocytosis of Candida albicans and differential cell counting. Nitric oxide (NO) production in serum, lung and spleen was measured with the Griess reaction. The mechanism involving p38 MAPK and IkappaB-alpha signal pathways was investigated by Western blot. RESULTS: Inflammatory changes of lung and spleen induced by LPS were alleviated by CCK-8, the increase of NO induced by LPS in serum, lung and spleen was significantly inhibited and the neutrophil infiltration in BAL was significantly reduced by CCK-8. The number of neutrophils was (52+/-10)X10(6) cells. (-1) in LPS group, while it decreased to (18+/-4)X10(6) cells. (-1) in CCK-8+LPS (P<0.01). The phagocytic rate of CCK-8 group increased to (62.49+/-9.49) %, compared with control group (48.16+/-14.20) %, P<0.05. The phagocytosis rate was (85.14+/-4.64) % in LPS group, which reduced to (59.33+/-3.14) % in CCK-8+LPS group (P<0.01). The results of phagocytosis indexes showed similar changes. CCK-8 may play an important role in increasing the expression of p38 MAPK and decreasing the degradation of IkappaB-alpha in lung and spleen of ES rats. CONCLUSION:CCK-8 can result in anti-inflammatory effects, which may be related to activation of p38 MAPK and inhibition on the degradation of IkappaB-alpha.
Authors: N Ohashi; A Matsumori; Y Furukawa; K Ono; M Okada; A Iwasaki; T Miyamoto; A Nakano; S Sasayama Journal: Arterioscler Thromb Vasc Biol Date: 2000-12 Impact factor: 8.311
Authors: Milena Bogunovic; Shaival H Davé; Jeremy S Tilstra; Diane T W Chang; Noam Harpaz; Huabao Xiong; Lloyd F Mayer; Scott E Plevy Journal: Am J Physiol Gastrointest Liver Physiol Date: 2007-03-29 Impact factor: 4.052
Authors: Susan C Tilton; Katrina M Waters; Norman J Karin; Bobbie-Jo M Webb-Robertson; Richard C Zangar; K Monica Lee; Diana J Bigelow; Joel G Pounds; Richard A Corley Journal: Toxicol Appl Pharmacol Date: 2013-01-07 Impact factor: 4.219