Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.2.3.23 (GAS)
 957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic gastritis induced by Helicobacter pylori is the strongest known risk factor for peptic ulceration and distal gastric cancer, and adherence of H. pylori to gastric epithelial cells is critical for induction of inflammation. One H. pylori constituent that increases disease risk is the cag pathogenicity island, which encodes a secretion system that translocates bacterial effector molecules into host cells. Decay-accelerating factor (DAF) is a cellular receptor for H. pylori and a mediator of the inflammatory response to this pathogen. H. pylori induces DAF expression in human gastric epithelial cells; therefore, we sought to define the mechanism by which H. pylori up-regulates DAF and to extend these findings into a murine model of H. pylori-induced injury. Co-culture of MKN28 gastric epithelial cells with the wild-type H. pylori cag(+) strain J166 induced transcriptional expression of DAF, which was attenuated by disruption of a structural component of the cag secretion system (cagE). H. pylori-induced expression of DAF was dependent upon activation of the p38 mitogen-activated protein kinase pathway but not NF-kappaB. Hypergastrinemic INS-GAS mice infected with wild-type H. pylori demonstrated significantly increased DAF expression in gastric epithelium versus uninfected controls or mice infected with an H. pylori cagE(-) isogenic mutant strain. These results indicate that H. pylori cag(+) strains induce up-regulation of a cognate cellular receptor in vitro and in vivo in a cag-dependent manner, representing the first evidence of regulation of an H. pylori host receptor by the cag pathogenicity island.
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PMID:Regulation of the Helicobacter pylori cellular receptor decay-accelerating factor. 1857 24

Earlier we have demonstrated that IL-12 p40 homodimer (p40(2)) induces the expression of inducible nitric oxide synthase (iNOS) in microglia. This study was undertaken to investigate underlying mechanisms required for IL-12 p40(2)- and IL-12 p70-induced expression of iNOS in microglia. IL-12 p40(2) alone induced the activation of both extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). Interestingly, the ERK pathway coupled p40(2) to iNOS expression via C/EBP beta, but not NF-kappaB, whereas the p38 pathway relayed the signal from p40(2) to iNOS expression via both NF-kappaB and C/EBP beta. Furthermore, by using microglia from IL-12R beta 1 (-/-) and IL-12R beta 2 (-/-) mice or siRNA against IL-12R beta 1 and IL-12R beta 2, we demonstrate that p40(2) induced the expression of iNOS in microglia via IL-12R beta 1-(ERK+p38)-(NF-kappaB +C/EBP beta) pathway. In contrast, both IL-12R beta 1 and IL-12R beta 2 were involved for IL-12 p70-induced microglial expression of iNOS. Although IL-12R beta 1 coupled p70 to NF-kappaB and C/EBP beta, IL-12R beta 2 was responsible for p70-mediated activation of GAS. This study delineates a new role of IL-12R beta 1 and IL-12R beta 2 for the expression of iNOS and production of NO in microglia that may participate in the pathogenesis of neuroinflammatory diseases.
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PMID:IL-12 p40 homodimer, the so-called biologically inactive molecule, induces nitric oxide synthase in microglia via IL-12R beta 1. 1930 59