Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite overwhelming evidence that enhanced production of the p75 tumor necrosis factor receptor (p75TNF-R) accompanies development of specific human inflammatory pathologies such as multi-organ failure during sepsis, inflammatory liver disease, pancreatitis, respiratory distress syndrome, or AIDS, the function of this receptor remains poorly defined in vivo. We show here that at levels relevant to human disease, production of the human p75TNF-R in transgenic mice results in a severe inflammatory syndrome involving mainly the pancreas, liver, kidney, and lung, and characterized by constitutively increased NF-kappaB activity in the peripheral blood mononuclear cell compartment. This process is shown to evolve independently of the presence of TNF, lymphotoxin alpha, or the p55TNF-R, although coexpression of a human TNF transgene accelerated pathology. These results establish an independent role for enhanced p75TNF-R production in the pathogenesis of inflammatory disease and implicate the direct involvement of this receptor in a wide range of human inflammatory pathologies.
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PMID:A critical role of the p75 tumor necrosis factor receptor (p75TNF-R) in organ inflammation independent of TNF, lymphotoxin alpha, or the p55TNF-R. 976 13

As a result of extensive clinical and basic research, the pivotal role of tumour necrosis factor (TNF) in the pathogenesis of chronic inflammatory diseases such as inflammatory bowel disease (IBD) has now generally been acknowledged. This has led to promising clinically effective anti-TNF-strategies. Of note, there is more and more evidence that TNF seems to play a key role in other gastrointestinal diseases including Helicobacter pylori infection, pancreatitis, viral hepatitis and toxic liver damage, too. The action of TNF at the cellular level is mediated by two cell surface receptors, TNF-R1 (p60) and TNF-R2 (p80). The function of these receptors and the downstream intracellular signal transduction pathway have been extensively studied in vitro and it can be expected, that there are critically important steps in TNF-signal transduction that might be dysregulated in these disease states. Their elucidation could lead to a better understanding of the pathogenesis of these diseases, in particular IBD and potentially reveal new, more specific therapeutic targets. Objective of this review is to give an overview about the current knowledge on TNF signal transduction in relationship to selected examples of important gastrointestinal disorders with special focus on IBD. Finally, the implications for future research efforts will be discussed.
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PMID:Functional relevance of soluble TNF-alpha, transmembrane TNF-alpha and TNF-signal transduction in gastrointestinal diseases with special reference to inflammatory bowel diseases. 1229 83