AIM: To investigate interleukin-18 (IL-18) in patients with chronic panreatitis (CP). METHODS: We studied 29 patients with CP and 30 healthy controls. Peripheral blood mononuclear cells (PBMC) were isolated an...AIM: To investigate interleukin-18 (IL-18) in patients with chronic panreatitis (CP). METHODS: We studied 29 patients with CP and 30 healthy controls. Peripheral blood mononuclear cells (PBMC) were isolated and incubated with 50 mmol/L ethanol, lipopolysaccharide (LPS) (doses 25 g/L, 250 g/L, 2500 g/L) and both agents for 24 h. Levels of IL-18 in the supernatants, and levels of IL-18, IL-12, interferon (IFN)-T and soluble CD14 in the serum were analysed by EI_ISA technique. Expression of IL-18 in PBMC was investigated by reverse-transcription (RT)-PCR. IL-18 protein levels in CP tissue and in normal pancreas were studied by ELISA technique. IL-18 levels in PBMC and pancreatic tissue were determined by Westernblot. Immunohistochemistry for pancreatic IL-18 expression was performed.RESULTS: In patients, IL-18 serum levels were significantly enhanced by 76% (mean: 289.9 ± 167.7 ng/L) compared with controls (mean: 165.2 ± 43.6 ng/L; P 〈 0.0005). IL-12 levels were enhanced by 25% in patients (18.3 ± 7.3 ng/L) compared with controls (14.7 ± 6.8 ng/L, P = 0.0576) although not reaching the statistical significance. IFN-γ, and soluble CD14 levels were not increased. In vitro, LPS stimulated significantly and dosedependently IL-18 secretion from PBMC. Incubation with ethanol reduced LPS-stimulated IL-18 secretion by about 50%. The mRNA expression of IL-18 in PBMC and the response of PBMC to ethanol and LPS was similar in CP patients and controls. In PBMC, no significant differences in IL-18 protein levels were detected between patients and controls. IL-18 protein levels were increased in CP tissues compared to normal pancreatic tissues. IL-18 was expressed by pancreatic acinar cells and by infiltrating inflammatory cells within the pancreas. CONCLUSION: IL-18 originates from the chronically inflammed pancreas and appears to be involved in the fibrotic destruction of the organ.展开更多
Color polymorphism offers rich opportunities for studying the eco-evolutionary mechanisms that drive the adaptations of local populations to heterogeneous and changing environments.We explored the color morph diversit...Color polymorphism offers rich opportunities for studying the eco-evolutionary mechanisms that drive the adaptations of local populations to heterogeneous and changing environments.We explored the color morph diversity and composition in a Chrysomela lapponica leaf beetle across its entire distribution range to test the hypothesis that environmental and climatic variables shape spatiotemporal variation in the phenotypic structure of a polymorphic species.We obtained information on 13617 specimens of this beetle from museums,private collections,and websites.These specimens(collected from 1830-2020)originated from 959 localities spanning 33°latitude,178°longitude,and 4200 m altitude.We classified the beetles into five color morphs and searched for environmental factors that could explain the variation in the level of polymorphism(quantified by the Shannon diversity index)and in the relative frequencies of individual color morphs.The highest level of polymorphism was found at high latitudes and altitudes.The color morphs differed in their climatic requirements;composition of colour morphs was independent of the geographic distance that separated populations but changed with collection year,longitude,mean July temperature and betweenyear temperature fluctuations.The proportion of melanic beetles,in line with the thermal melanism hypothesis,increased with increasing latitude and altitude and decreased with increasing climate seasonality.Melanic morph frequencies also declined during the past century,but only at high latitudes and altitudes where recent climate warming was especially strong.The observed patterns suggest that color polymorphism is especially advantageous for populations inhabiting unpredictable environments,presumably due to the different climatic requirements of coexisting color morphs.展开更多
基金Supported by a grant to MVS, Forschungsfonds, project number 098200/99-234, Faculty of Clinical Medicine, University of Heidelberg at Mannheim, Germany by a grant "Landesforschungsschwerpunkt-Molekulare Mechanismen alkoholassoziierter Erkrankungen", project number 23-7532, Baden-Württemberg, Germany and by the Dietmar-Hopp-Foundation, Walldorf, Germany
文摘AIM: To investigate interleukin-18 (IL-18) in patients with chronic panreatitis (CP). METHODS: We studied 29 patients with CP and 30 healthy controls. Peripheral blood mononuclear cells (PBMC) were isolated and incubated with 50 mmol/L ethanol, lipopolysaccharide (LPS) (doses 25 g/L, 250 g/L, 2500 g/L) and both agents for 24 h. Levels of IL-18 in the supernatants, and levels of IL-18, IL-12, interferon (IFN)-T and soluble CD14 in the serum were analysed by EI_ISA technique. Expression of IL-18 in PBMC was investigated by reverse-transcription (RT)-PCR. IL-18 protein levels in CP tissue and in normal pancreas were studied by ELISA technique. IL-18 levels in PBMC and pancreatic tissue were determined by Westernblot. Immunohistochemistry for pancreatic IL-18 expression was performed.RESULTS: In patients, IL-18 serum levels were significantly enhanced by 76% (mean: 289.9 ± 167.7 ng/L) compared with controls (mean: 165.2 ± 43.6 ng/L; P 〈 0.0005). IL-12 levels were enhanced by 25% in patients (18.3 ± 7.3 ng/L) compared with controls (14.7 ± 6.8 ng/L, P = 0.0576) although not reaching the statistical significance. IFN-γ, and soluble CD14 levels were not increased. In vitro, LPS stimulated significantly and dosedependently IL-18 secretion from PBMC. Incubation with ethanol reduced LPS-stimulated IL-18 secretion by about 50%. The mRNA expression of IL-18 in PBMC and the response of PBMC to ethanol and LPS was similar in CP patients and controls. In PBMC, no significant differences in IL-18 protein levels were detected between patients and controls. IL-18 protein levels were increased in CP tissues compared to normal pancreatic tissues. IL-18 was expressed by pancreatic acinar cells and by infiltrating inflammatory cells within the pancreas. CONCLUSION: IL-18 originates from the chronically inflammed pancreas and appears to be involved in the fibrotic destruction of the organ.
基金Collection of the substantial part of the data and the completion of the study were supported by the Academy of Finland(projects 122133,122144,122180,127047,203156,208016,214653,268124,276671,311929,and 316182)L.S.was supported by the Ministry of Culture of the Czech Republic(DKRVO 2019-2023/5.1.b,National Museum,00023272)+1 种基金V.L.was supported by the Czech Academy of Sciences(RVO 679859939)Z.O.was supported by the Erasmus+programme of the European Union.
文摘Color polymorphism offers rich opportunities for studying the eco-evolutionary mechanisms that drive the adaptations of local populations to heterogeneous and changing environments.We explored the color morph diversity and composition in a Chrysomela lapponica leaf beetle across its entire distribution range to test the hypothesis that environmental and climatic variables shape spatiotemporal variation in the phenotypic structure of a polymorphic species.We obtained information on 13617 specimens of this beetle from museums,private collections,and websites.These specimens(collected from 1830-2020)originated from 959 localities spanning 33°latitude,178°longitude,and 4200 m altitude.We classified the beetles into five color morphs and searched for environmental factors that could explain the variation in the level of polymorphism(quantified by the Shannon diversity index)and in the relative frequencies of individual color morphs.The highest level of polymorphism was found at high latitudes and altitudes.The color morphs differed in their climatic requirements;composition of colour morphs was independent of the geographic distance that separated populations but changed with collection year,longitude,mean July temperature and betweenyear temperature fluctuations.The proportion of melanic beetles,in line with the thermal melanism hypothesis,increased with increasing latitude and altitude and decreased with increasing climate seasonality.Melanic morph frequencies also declined during the past century,but only at high latitudes and altitudes where recent climate warming was especially strong.The observed patterns suggest that color polymorphism is especially advantageous for populations inhabiting unpredictable environments,presumably due to the different climatic requirements of coexisting color morphs.