Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophil adhesion to extracellular matrix is necessary for an effective inflammatory response. Adhesion may accelerate neutrophil activation by affecting intracellular signaling pathways. The nuclear transcription factor kappaB (NF-kappaB) controls several cellular functions, including inflammation, proliferation, and cell survival. We explored the role of adhesion in NF-kappaB activation in human neutrophils. Cells were stimulated with tumor necrosis factor-alpha (TNF-alpha), granulocyte macrophage-colony-stimulating factor (GM-CSF), interleukin-8 (IL-8), and formyl-methionyl-leucyl-phenylalanine (fMLP). All four initiated neutrophil adherence to and spreading on fibronectin. GM-CSF and IL-8 did not activate NF-kappaB in suspended neutrophils but rapidly activated NF-kappaB under adherent conditions on matrix, as shown by IkappaB kinase activity assay, IkappaBalpha degradation, electromobility shift assay, and quantitative reverse transcriptase-PCR. In contrast, TNF-alpha activated NF-kappaB both in suspended cells and adherent cells. fMLP did not activate NF-kappaB in either suspended or adherent cells. Specific beta(2) integrin blockade prevented NF-kappaB activation by GM-CSF and IL-8 on fibronectin. Co-stimulating CD18 and CD11b with activating antibodies resulted in NF-kappaB activation by GM-CSF and IL-8 in suspended cells. We inhibited actin polymerization with cytochalasin and blocked the non-receptor kinase Syk with piceatannol. Both maneuvers prevented the co-stimulatory NF-kappaB-activating signal by beta(2) integrins. Thus, in addition to beta(2) integrin ligand binding, NF-kappaB activation depended on the formation of the receptor-associated intracellular focal adhesion complex. We conclude that beta(2) integrins may provide co-stimulatory signals allowing some soluble mediators to activate the NF-kappaB pathway even when they are not capable of doing so in suspension. This effect may become important when human neutrophils leave the circulating blood and migrate through extracellular matrix during inflammation.
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PMID:Integrins and cytokines activate nuclear transcription factor-kappaB in human neutrophils. 1461 35

Adhesion molecules play an important role in the development of atherogenesis and are produced by endothelial cells after being stimulated with various inflammatory cytokines. This study examined the effect of saponins that were isolated from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil saponins (CKS), on the cytokine-induced monocyte/human endothelial cell interaction, which is a crucial early event in atherogenesis. CKS significantly inhibited the TNFalpha-induced increase in monocyte adhesion to endothelial cells as well as decreased the protein and mRNA expression levels of vascular adhesion molecule-1 and intercellular cell adhesion molecule-1 on endothelial cells. Furthermore, CKS significantly inhibited the TNFalpha-induced production of intracellular reactive oxygen species (ROS) and activation of NF-kappaB by preventing IkappaB degradation and inhibiting IkappaB kinase activity. Overall, CKS has anti-atherosclerotic and anti-inflammatory activity, which is least in part the result of it reducing the cytokine-induced endothelial adhesion to monocytes by inhibiting intracellular ROS production, NF-kappaB activation, and cell adhesion molecule expression in endothelial cells.
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PMID:Inhibition of tumor necrosis factor-alpha-induced expression of adhesion molecules in human endothelial cells by the saponins derived from roots of Platycodon grandiflorum. 1627 38

Nuclear factor-kappaB (NF-kappaB) has an important role in multiple myeloma (MM) cell pathogenesis in the context of the bone marrow (BM) microenvironment. In NF-kappaB signaling cascades, IkappaB kinase alpha (IKKalpha) and IKKbeta are key molecules that predominantly mediate noncanonical and canonical pathways, respectively. In this study, we examined the biologic sequelae of the inhibition of IKKalpha versus IKKbeta in MM cell lines. All MM cell lines have constitutive canonical NF-kappaB activity, and a subset of MM cell lines shows noncanonical NF-kappaB activity. Adhesion to BM stromal cells further activates both canonical and noncanonical NF-kappaB activity. IKKbeta inhibitor MLN120B blocks canonical pathway and growth of MM cell lines but does not inhibit the noncanonical NF-kappaB pathway. Although IKKalpha knockdown induces significant growth inhibition in the cell lines with both canonical and noncanonical pathways, it does not inhibit NF-kappaB activation. Importantly, IKKalpha down-regulation decreases expression of beta-catenin and aurora-A, which are known to mediate MM cell growth and survival. Finally, IKKbeta inhibitor enhances the growth inhibition triggered by IKKalpha down-regulation in MM cells with both canonical and noncanonical NF-kappaB activity. Combination therapy targeting these kinases therefore represents a promising treatment strategy in MM.
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PMID:Biologic sequelae of I{kappa}B kinase (IKK) inhibition in multiple myeloma: therapeutic implications. 1927 Feb 64