Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colony-stimulating factor (CSF)-1 is a hematopoietic growth factor that is released by osteoblasts and is recognized to play a critical role in bone remodeling in vivo and in vitro. We have reported that osteoblasts express CSF-1 constitutively and that tumor necrosis factor (TNF)-alpha, a potent bone-resorbing agent, increases CSF-1 gene expression by a transcriptional mechanism. In the present study, we report that an NF-kappaB site in the CSF-1 promoter is required for TNF-alpha-induced CSF-1 expression in osteoblasts. As determined by electrophoretic mobility shift assays, antiserum against the NF-kappaB-binding protein, p50, retarded the mobility of the inducible complex, whereas antisera against p52, p65, c-Rel, Rel B, IkappaB alpha, IkappaB gamma, and Bcl-3 had no effect. To further confirm that p50 is necessary for TNF-alpha-induced CSF-1 expression in osteoblasts, CSF-1 messenger RNA expression from untreated and TNF-alpha-treated osteoblasts, prepared from wild-type and p50 knock-out mice, was examined by Northern analysis. CSF-1 messenger RNA was increased by TNF treatment in wild-type mice but not in NF-kappaB p50 knock-out mice. Our findings support the conclusion that the NF-kappaB subunit p50 is critical for TNF-induced CSF-1 expression in osteoblasts.
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PMID:Nuclear factor-kappaB p50 is required for tumor necrosis factor-alpha-induced colony-stimulating factor-1 gene expression in osteoblasts. 1091 79

This study investigated for the first time the effects of the cis isomer of RESV (c-RESV), a polyphenol present in red wine, on an array of genes whose expression is controlled by nuclear factor kappa B (NF-kappaB) and whose transcriptional activation is critical in a number of pathologies (including some cardiovascular diseases). In inflammatory peritoneal macrophages stimulated with lipopolysaccharide (LPS) and gamma interferon (IFN-gamma), c-RESV significantly blocked the expression of genes related to the REL/NF-kappaB/IkappaB family, adhesion molecules and acute-phase proteins; however, the greatest modulatory effect was obtained on the expression of genes related to the pro-inflammatory cytokines. c-RESV down-regulated the nuclear factor of kappa light chain gene enhancer in B-cells 1 (NFkappaBL1) gene product p105 and up-regulated the nuclear factor of kappa light chain gene enhancer in B-cells inhibitor alpha (IkappaBalpha) gene. c-RESV also significantly inhibited intercellular adhesion molecule-1 (ICAM-1) gene expression and the transmembrane receptors RIP (receptor TNFRSF) and TLR3 (toll-like receptor 7). At 100 muM, c-RESV significantly inhibited transcription of Scya2 (chemokine MCP-1), the chemokine RANTES (regulated on activation, normal T cell expressed and secreted), pro-inflammatory cytokines that attract monocyte-granulocyte cells such as M-CSF (colony-stimulating factor 1), GM-CSF (colony-stimulating factor 2) and G-CSF (colony-stimulating factor 3), the cytokine tumor growth factor beta (TGF-beta) and the extracellular ligand IL-1alpha. In contrast, c-RESV stimulated transcription of the pro-inflammatory cytokines IL-6 and tumor necrosis factor alpha (TNF-alpha), the extracellular ligand IL-1beta, and the IFN regulatory factor (IRF)-1. In conclusion, c-RESV has a significant modulatory effect on the NF-kappaB signaling pathway and, consequently, an important antioxidant role that may partially explain the cardioprotective effects attributed to long-term moderate red wine consumption.
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PMID:Effect of cis-resveratrol on genes involved in nuclear factor kappa B signaling. 1565 68