Advances in understanding the interaction between the human immune system and the microbiome have led to an improved understanding of the function of the vermiform appendix as a safe-house for beneficial bacteria in t...Advances in understanding the interaction between the human immune system and the microbiome have led to an improved understanding of the function of the vermiform appendix as a safe-house for beneficial bacteria in the colon.These advances have been made despite long standing clinical observations that the appendectomy is a safe and effective procedure.However,more recent clinical data show that an appendectomy puts patients at increased risk for recurrent Clostridium difficile(C.difficile)-associated colitis,and probably other diseases associated with an altered microbiome.At the same time,appendectomy does not apparently put patients at risk for an initial onset of C.difficile-associated colitis.These clinical observations point toward the idea that the vermiform appendix might not effectively protect the microbiome in the face of broad spectrum antibiotics,the use of which precedes the initial onset of C.difficile-associated colitis.Further,these observations point to the idea that historically important threats to the microbiome such as infectious gastrointestinal pathogens have been supplanted by other threats,particularly the use of broad spectrum antibiotics.展开更多
Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancrea...Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pan-creatitis characterized by marked stroma formation with a high number of infiltrating granulocytes(such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells(PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in pro-moting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways(i.e., Transforming growth factor-β/SMAD, mitogen--activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin(IL)-1, IL-1β, IL-6, IL--8 IL-10, IL-18, IL--33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for pancreatic pathogenesis.展开更多
文摘Advances in understanding the interaction between the human immune system and the microbiome have led to an improved understanding of the function of the vermiform appendix as a safe-house for beneficial bacteria in the colon.These advances have been made despite long standing clinical observations that the appendectomy is a safe and effective procedure.However,more recent clinical data show that an appendectomy puts patients at increased risk for recurrent Clostridium difficile(C.difficile)-associated colitis,and probably other diseases associated with an altered microbiome.At the same time,appendectomy does not apparently put patients at risk for an initial onset of C.difficile-associated colitis.These clinical observations point toward the idea that the vermiform appendix might not effectively protect the microbiome in the face of broad spectrum antibiotics,the use of which precedes the initial onset of C.difficile-associated colitis.Further,these observations point to the idea that historically important threats to the microbiome such as infectious gastrointestinal pathogens have been supplanted by other threats,particularly the use of broad spectrum antibiotics.
基金Supported by National Institutes of Health,Nos.R01 DK067255 and R01 AI080581
文摘Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pan-creatitis characterized by marked stroma formation with a high number of infiltrating granulocytes(such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells(PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in pro-moting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways(i.e., Transforming growth factor-β/SMAD, mitogen--activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin(IL)-1, IL-1β, IL-6, IL--8 IL-10, IL-18, IL--33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for pancreatic pathogenesis.
