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Molecular Mechanism of beta1 Integrin Signal Transduction.
The interaction between the extracellular matrix and cells affects a wide spectrum of cellular processes including migration, growth, death, capacity to degrade matrix, capacity to synthesize matrix, differentiation, and cell
attachment. In human neutrophils, we study signalling by beta1 integrin receptors which contribute to cell attachment and migration. Additionally, we study the effect of nitric oxide, an inflammatory mediator, on the signalling
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Neutrophils help destroy foreign invaders at tissue sites but first must reversibly undergo cell attachment through the endothelium and matrix. We hypothesize that nitric oxide modulates matrix-cell interaction by the reversible inhibition of neutrophil attachment to fibronectin (ligand for beta1 integrin)-coated surfaces. We recently showed that nitric oxide inhibits adherence associated with a stimulation of actin-ADP ribosylation. In bovine chondrocytes, we study signalling by beta1 integrin receptors which contribute to the capacity to degrade matrix and differentiation. We hypothesize that nitric oxide, a mediator of arthritis, inhibits chondrocyte adherence and cell capacity to contribute to matrix synthesis and breakdown. Recently, we studied signalling by beta1 integrins in chondrocytes by measuring protein accumulation to contact sites in chondrocytes exposed to fibronectin-coated and albumin-coated beads. Chondrocytes exposed to albumin-coated beads failed to generate a response, but cytoskeletal and signalling molecules accumulated to fibronectin. Summary of results of recent studies which examined the accumulation of cytoskeletal (f–actin) and signalling proteins [low molecular weight G protein (rho) and focal adhesion kinase (FAK)] to contact sites by chondrocytes exposed to fibronectin–coated beads. Nitric oxide inhibits beta1 integrin signalling in chondrocytes. Prior exposure of chondrocytes to catabolic cytokines, which stimulates nitric oxide synthesis, inhibits transduction process. Conclusion: oxide inhibits beta1 integrin signalling in chondrocytes. |
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