Inflammatory bowel diseases(IBD) are a complex group of diseases involving alterations in mucosal immunity and gastrointestinal physiology during both initiation and progressive phases of the disease.At the core of th...Inflammatory bowel diseases(IBD) are a complex group of diseases involving alterations in mucosal immunity and gastrointestinal physiology during both initiation and progressive phases of the disease.At the core of these alterations are endothelial cells,whose continual adjustments in structure and function coordinate vascular supply,immune cell emigration,and regulation of the tissue environment.Expansion of the endothelium in IBD(angiogenesis),mediated by inflammatory growth factors,cytokines and chemokines,is a hallmark of active gut disease and is closely related to disease severity.The endothelium in newly formed or inflamed vessels differs from that in normal vessels in the production of and response to inflammatory cytokines,growth factors,and adhesion molecules,altering coagulant capacity,barrier function and blood cell recruitment in injury.This review examines the roles of the endothelium in the initiation and propagation of IBD pathology and distinctive features of the intestinal endothelium contributing to these conditions.展开更多
Inflammatory bowel disease(IBD)is a common and lifelong disabling gastrointestinal disease.Emerging treatments are being developed to target inflammatory cytokines which initiate and perpetuate the immune response.Ade...Inflammatory bowel disease(IBD)is a common and lifelong disabling gastrointestinal disease.Emerging treatments are being developed to target inflammatory cytokines which initiate and perpetuate the immune response.Adenosine is an important modulator of inflammation and its anti-inflammatory effects have been well established in humans as well as in animal models.High extracellular adenosine suppresses and resolves chronic inflammation in IBD models.High extracellular adenosine levels could be achieved by enhanced adenosine absorption and increased de novo synthesis.Increased adenosine concentration leads to activation of the A2a receptor on the cell surface of immune and epithelial cells that would be a potential therapeutic target for chronic intestinal inflammation. Adenosine is transported via concentrative nucleoside transporter and equilibrative nucleoside transporter transporters that are localized in apical and basolateral membranes of intestinal epithelial cells,respectively. Increased extracellular adenosine levels activate the A2a receptor,which would reduce cytokines responsible for chronic inflammation.展开更多
Toll-like receptors （TLRs） are probably the most important class of pattern-recognition receptors. Members of the TLR family play key roles in the both innate and adaptive immune responses. Recognition of pathogen-a...Toll-like receptors （TLRs） are probably the most important class of pattern-recognition receptors. Members of the TLR family play key roles in the both innate and adaptive immune responses. Recognition of pathogen-associated molecular patterns （PAMPs） by TLRs, either alone or in heterodimedzation with other TLR or non-TLR receptors, induces the production of signals that are responsible for the activation of genes important for an effective host defense, especially those of proinflammatory cytokines. Thus, TLRs are involved in the development of many pathological conditions including infectious diseases, tissue damage, and cancer especially. In this review, the contribution of TLRs to tumorgenesis is evaluated. We hope to provide new insight into the progression of cancer and more importantly into the potential for TLRs as targets of therapeutics.展开更多
基金Supported by National Institute of Health,NIH DK 43785
文摘Inflammatory bowel diseases(IBD) are a complex group of diseases involving alterations in mucosal immunity and gastrointestinal physiology during both initiation and progressive phases of the disease.At the core of these alterations are endothelial cells,whose continual adjustments in structure and function coordinate vascular supply,immune cell emigration,and regulation of the tissue environment.Expansion of the endothelium in IBD(angiogenesis),mediated by inflammatory growth factors,cytokines and chemokines,is a hallmark of active gut disease and is closely related to disease severity.The endothelium in newly formed or inflamed vessels differs from that in normal vessels in the production of and response to inflammatory cytokines,growth factors,and adhesion molecules,altering coagulant capacity,barrier function and blood cell recruitment in injury.This review examines the roles of the endothelium in the initiation and propagation of IBD pathology and distinctive features of the intestinal endothelium contributing to these conditions.
基金Supported by A research grant(DK-018777)from the National Institute of Diabetes and Digestive and Kidney Diseases
文摘Inflammatory bowel disease(IBD)is a common and lifelong disabling gastrointestinal disease.Emerging treatments are being developed to target inflammatory cytokines which initiate and perpetuate the immune response.Adenosine is an important modulator of inflammation and its anti-inflammatory effects have been well established in humans as well as in animal models.High extracellular adenosine suppresses and resolves chronic inflammation in IBD models.High extracellular adenosine levels could be achieved by enhanced adenosine absorption and increased de novo synthesis.Increased adenosine concentration leads to activation of the A2a receptor on the cell surface of immune and epithelial cells that would be a potential therapeutic target for chronic intestinal inflammation. Adenosine is transported via concentrative nucleoside transporter and equilibrative nucleoside transporter transporters that are localized in apical and basolateral membranes of intestinal epithelial cells,respectively. Increased extracellular adenosine levels activate the A2a receptor,which would reduce cytokines responsible for chronic inflammation.
文摘Toll-like receptors （TLRs） are probably the most important class of pattern-recognition receptors. Members of the TLR family play key roles in the both innate and adaptive immune responses. Recognition of pathogen-associated molecular patterns （PAMPs） by TLRs, either alone or in heterodimedzation with other TLR or non-TLR receptors, induces the production of signals that are responsible for the activation of genes important for an effective host defense, especially those of proinflammatory cytokines. Thus, TLRs are involved in the development of many pathological conditions including infectious diseases, tissue damage, and cancer especially. In this review, the contribution of TLRs to tumorgenesis is evaluated. We hope to provide new insight into the progression of cancer and more importantly into the potential for TLRs as targets of therapeutics.
