Cytokines in context.

Nathan, Carl; Sporn, Michael B.

doi:10.1083/jcb.113.5.981

Cited by 773 publications

(310 citation statements)

References 79 publications

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“…These signals can be generated by (and their biological nature determined by) products of the migrating leukocytes themselves (e.g., cytokines, chemokines, growth factors, and enzymes) from the ECM (e.g., intact, degraded immobilized, or degraded soluble components), or, as shown here, products of the enzymatic degradation of inflammatory cytokines. During migration, leukocytes, especially T cells, can encounter, either sequentially or simultaneously, several of these soluble or immobilized modulators (3,(21)(22)(23), whereupon the chemical complexity of these signals is increased. Recently, we isolated, sequenced, and synthesized peptides resulting from the degradation of IL-2 by human neutrophil elastase (4).…”

Section: Discussionmentioning

confidence: 99%

“…Molecular interactions with such receptors, which influence the activation, adhesion, and migration of immune cells, are affected by inflammatory-regulating signals (21). These signals can be generated by (and their biological nature determined by) products of the migrating leukocytes themselves (e.g., cytokines, chemokines, growth factors, and enzymes) from the ECM (e.g., intact, degraded immobilized, or degraded soluble components), or, as shown here, products of the enzymatic degradation of inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

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Cell Surface-Expressed Moesin-Like Receptor Regulates T Cell Interactions with Tissue Components and Binds an Adhesion-Modulating IL-2 Peptide Generated by Elastase

Ariel

Hershkoviz

Altbaum-Weiss

et al. 2001

The Journal of Immunology

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The adhesion of leukocytes to the extracellular matrix (ECM) depends on their responses to variations in the chemotactic signals in their milieu, as well as on the functioning of cytoskeletal and context-specific receptors. Ezrin, radixin, and moesin constitute a family of proteins that link the plasma membrane to the actin cytoskeleton. The surface expression of moesin on T cells and its role in cell adhesion has not been fully elucidated. Recently, we found that IL-2 peptides generated by elastase modified the adhesion of activated T cells to ECM ligands. Here, we further examined the adhesion regulatory effects of EFLNRWIT, one of the IL-2 peptides, as well as the existence and putative function of its receptor on T cells. We found that when presented to T cells in the absence of another activator, the EFLNRWIT peptide induced cell adhesion to vessel wall and ECM components. Binding of a radiolabeled peptide to T cells, precipitation with the immobilized peptide, and amino acid sequencing of the precipitated protein revealed that EFLNRWIT exerts its function via a cell surface-expressed moesin-like moiety, whose constitutive expression on T cells was increased after activation. This notion was further supported by our findings that: 1) anti-moesin mAb inhibited the binding of T cells to the immobilized EFLNRWIT peptide, 2) immobilized recombinant moesin bound the IL-2 peptide, and 3) soluble moesin inhibited the EFLNRWIT-induced T cell adhesion to fibronectin. Interestingly, moesin appears to be generally involved in T cell responses to adhesion-regulating signals. Thus, the IL-2 peptide EFLNRWIT appears to exert its modulating capacities via an adhesion-regulating moesin-like receptor.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cell Surface-Expressed Moesin-Like Receptor Regulates T Cell Interactions with Tissue Components and Binds an Adhesion-Modulating IL-2 Peptide Generated by Elastase

Ariel

Hershkoviz

Altbaum-Weiss

et al. 2001

The Journal of Immunology

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“…Cytokines are used as autocrine, paracrine, and endocrine signals by a cell communicating with its environment to ensure a homeostatic balance [3]. Thus, cytokines are important intermediators between cells and their ECM, because certain cell-matrix interactions can induce the production of cytokines, and cytokines can induce alterations in composition of the ECM [4].…”

Section: The Role Of Cytokines In Renal Diseasementioning

confidence: 99%

ECM homeostasis in renal diseases: a genomic approach

Eikmans

Baelde

Heer

et al. 2003

The Journal of Pathology

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Chronic renal disease is in general histologically accompanied by a vast amount of scar tissue, ie glomerulosclerosis and interstitial fibrosis. Scarring results from excessive accumulation of extracellular matrix (ECM) components, a process driven by a plethora of cytokines and growth factors. Studies in experimental renal disease which target these regulators using gene therapy limit or prevent the development of scarring. This review focuses specifically on the role of transforming growth factor-beta, platelet-derived growth factor, connective tissue growth factor, hepatocyte growth factor, and epidermal growth factor. The results obtained in animal models hold promise for molecular intervention strategies in human renal disease. Microarray technology allows large-scale gene expression profiling in kidney tissue to identify common molecular pathways in a step towards discovery of new drug targets. Molecular techniques are expected to be used for diagnostic and prognostic purposes in nephrological practice to supplement renal biopsy. Several studies already show that molecular techniques might be of use in routine diagnostic practice. Improvement of diagnosis and prediction of outcome in renal patients might lead to more efficient and earlier therapeutic intervention.

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“…Although much work in understanding growth factor regulation has been accomplished in recent years with regard to the transcriptional control of growth factor expression, the studies described in this review and elsewhere (Nathan and Sporn, 1991) suggest that regulation of growth factor activity cannot be understood solely at the level of expression. For example, it is our opinion that an increase in the expression of a latent growth factor, such as latent TGF-#, is not likely to impact directly on cell function because the latent factor is already present in plasma at a concentration above that necessary to elicit maximal biological activity.…”

Section: Extracellular Matrixmentioning

confidence: 99%