SMAD4 Is Required for Development of Maximal Endotoxin Tolerance
نویسندگان
چکیده
منابع مشابه
SMAD4 is required for development of maximal endotoxin tolerance.
Initial exposure of monocytes/macrophages to LPS induces hyporesponsiveness to a second challenge with LPS, a phenomenon termed LPS tolerance. Molecular mechanisms responsible for endotoxin tolerance are not well defined. We and others have shown that IL-1R-associated kinase (IRAK)-M and SHIP-1 proteins, negative regulators of TLR4 signaling, increase in tolerized cells. TGF-beta1, an anti-infl...
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Endotoxin tolerance allows macrophages to produce large quantities of proinflammatory cytokines immediately after their contact with lipopolysaccharides (LPSs), but prevents their further production after repeated exposure to LPSs. While this response is known to prevent overproduction of proinflammatory cytokines, the mechanism through which endotoxin tolerance is established has not been iden...
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Bone homeostasis is maintained as a delicate balance between bone-resorption and bone-formation, which are coupled to maintain appropriate bone mass. A critical question is how bone-resorption is terminated to allow bone-formation to occur. Here, we show that TGFβs inhibit osteoclastogenesis and maintain bone-mass through Smad4 activity in osteoclasts. We found that latent-TGFβ1 was activated b...
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Mutations in the SMAD4/DPC4 tumor suppressor gene, a key signal transducer in most TGFbeta-related pathways, are involved in 50% of pancreatic cancers. Homozygous Smad4 mutant mice die before day 7.5 of embryogenesis. Mutant embryos have reduced size, fail to gastrulate or express a mesodermal marker, and show abnormal visceral endoderm development. Growth retardation of the Smad4-deficient emb...
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Healthy male volunteers were rendered tolerant to the pyrogenic and toxic activities of bacterial endotoxin by daily intravenous injections. Five subjects were given 0.5 microg Salmonella typhosa endotoxin for 7 days; four subjects were given Pseudomonas endotoxin, increasing over a period of 30 days from 25 to 250 microg. Reticuloendothelial system (RES) phagocytic activity was assessed by ser...
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ژورنال
عنوان ژورنال: The Journal of Immunology
سال: 2010
ISSN: 0022-1767,1550-6606
DOI: 10.4049/jimmunol.0901601