The ‘‘omics sciences’’ (genomics, transcriptomics, proteomics) are often used to study living organisms as a whole system by evaluating the complex expression patterns o...The ‘‘omics sciences’’ (genomics, transcriptomics, proteomics) are often used to study living organisms as a whole system by evaluating the complex expression patterns of genes, miRNA, proteins, and metabolites. This study aimed, through bioinformatics and systems biology, to decipher the cytokinome profile in the evolution of inflammatory processes leading to cancer. The cytokinome was defined as the totality of cytokines and their interactions in and around biological cells. The system biology approach would provide a better understanding of the complex interaction network of cytokines, especially in cancer patients. Acquired knowledge would enable health providers with tools to evaluate disease onset through progression as well as identifying innovative therapeutic strategies. Understanding the role each cytokine plays in the metabolic network is of great importance. This paper reviews our group’s ‘‘omics’’ work. In particular, it addresses the role cytokines play in liver disease in six different scenarios. The first is the role the cytokines play in chronic inflammatory diseases and cancers. The second is the significance of the cytokinome profile. The third is the role of liver cirrhosis as an inflammatory disease. The fourth is the comparison of cytokine levels evaluated in patients with chronic hepatitis C virus (HCV) or with HCV-related cirrhosis. The fifth is the comparison of cytokine levels evaluated in patients with HCV-related cirrhosis in the presence and absence of type 2 diabetes. And lastly, we present a comparison of cytokine levels evaluated in patients with HCV-related cirrhosis in the presence and absence of hepatocellular carcinoma.展开更多
Background: Being non-immunogenic and capable of achieving major metabolic liver functions, adult-derived human liver stem/progenitor cells (ADHLSCs) are of special interest in the field of liver cell therapy. The cyt...Background: Being non-immunogenic and capable of achieving major metabolic liver functions, adult-derived human liver stem/progenitor cells (ADHLSCs) are of special interest in the field of liver cell therapy. The cytokine repertoire of engrafted cells may have critical impacts on the immune response balance, particularly during cell transplantation. Methods: In this work, we analyzed the cytokinome of ADHLSCs during hepatogenic differentiation (HD) following stimulation with a mixture of inflammatory cytokines (I) in vitro and compared it to that of mature hepatocytes. Results: Independent of their hepatic state, ADHLSCs showed no constitutive expression of pro-inflammatory cytokines, which were significantly induced by inflammation (IL-1β, IL-6, IL-8, TNFα, CCL5, IL-12a, IL-12b, IL-23p19, IL-27p28 and EBI-3). IL1-RA and IDO-1, as immunoregulatory cytokines, were highly induced in undifferentiated ADHLSCs, whereas TGF-β was downregulated by both hepatic and inflammatory events. Interestingly, TDO-1 was exclusively expressed in ADHLSCs after hepatic differentiation and enhanced by inflammatory cytokines. Compared to mature hepatocytes, hepatic-differentiated ADHLSCs showed significantly different cytokine expression patterns. Conclusions: By establishing the cytokinome of ADHLSCs and highlighting their immunological and inflammatory features, we can enhance our knowledge about the safety and efficiency of the transplantation strategy.展开更多
文摘The ‘‘omics sciences’’ (genomics, transcriptomics, proteomics) are often used to study living organisms as a whole system by evaluating the complex expression patterns of genes, miRNA, proteins, and metabolites. This study aimed, through bioinformatics and systems biology, to decipher the cytokinome profile in the evolution of inflammatory processes leading to cancer. The cytokinome was defined as the totality of cytokines and their interactions in and around biological cells. The system biology approach would provide a better understanding of the complex interaction network of cytokines, especially in cancer patients. Acquired knowledge would enable health providers with tools to evaluate disease onset through progression as well as identifying innovative therapeutic strategies. Understanding the role each cytokine plays in the metabolic network is of great importance. This paper reviews our group’s ‘‘omics’’ work. In particular, it addresses the role cytokines play in liver disease in six different scenarios. The first is the role the cytokines play in chronic inflammatory diseases and cancers. The second is the significance of the cytokinome profile. The third is the role of liver cirrhosis as an inflammatory disease. The fourth is the comparison of cytokine levels evaluated in patients with chronic hepatitis C virus (HCV) or with HCV-related cirrhosis. The fifth is the comparison of cytokine levels evaluated in patients with HCV-related cirrhosis in the presence and absence of type 2 diabetes. And lastly, we present a comparison of cytokine levels evaluated in patients with HCV-related cirrhosis in the presence and absence of hepatocellular carcinoma.
文摘Background: Being non-immunogenic and capable of achieving major metabolic liver functions, adult-derived human liver stem/progenitor cells (ADHLSCs) are of special interest in the field of liver cell therapy. The cytokine repertoire of engrafted cells may have critical impacts on the immune response balance, particularly during cell transplantation. Methods: In this work, we analyzed the cytokinome of ADHLSCs during hepatogenic differentiation (HD) following stimulation with a mixture of inflammatory cytokines (I) in vitro and compared it to that of mature hepatocytes. Results: Independent of their hepatic state, ADHLSCs showed no constitutive expression of pro-inflammatory cytokines, which were significantly induced by inflammation (IL-1β, IL-6, IL-8, TNFα, CCL5, IL-12a, IL-12b, IL-23p19, IL-27p28 and EBI-3). IL1-RA and IDO-1, as immunoregulatory cytokines, were highly induced in undifferentiated ADHLSCs, whereas TGF-β was downregulated by both hepatic and inflammatory events. Interestingly, TDO-1 was exclusively expressed in ADHLSCs after hepatic differentiation and enhanced by inflammatory cytokines. Compared to mature hepatocytes, hepatic-differentiated ADHLSCs showed significantly different cytokine expression patterns. Conclusions: By establishing the cytokinome of ADHLSCs and highlighting their immunological and inflammatory features, we can enhance our knowledge about the safety and efficiency of the transplantation strategy.
