Augmentation of RANTES-Induced Extracellular Signal-Regulated Kinase Mediated Signaling and T Cell Adhesion by Elastase-Treated Fibronectin

Brill, Alexander; Hershkoviz, Rami; Vaday, Gayle G.; Chowers, Yehuda; Lider, Ofer

doi:10.4049/jimmunol.166.12.7121

Cited by 17 publications

(9 citation statements)

References 37 publications

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“…Recent evidence suggests that inflammatory cell adhesion is mediated at least in part by MEK/ERK pathway activation (32,33). Results concerning p38 involvement differ depending on the cell and the conditions studied (32,34).…”

Section: Discussionmentioning

confidence: 91%

Thrombin Induces Mast Cell Adhesion to Fibronectin: Evidence for Involvement of Protease-Activated Receptor-1

Vliagoftis

2002

The Journal of Immunology

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Thrombin activates mast cells to release inflammatory mediators through a mechanism involving protease-activated receptor-1 (PAR-1). We hypothesized that PAR-1 activation would induce mast cell adhesion to fibronectin (FN). Fluorescent adhesion assay was performed in 96-well plates coated with FN (20 μg/ml). Murine bone marrow cultured mast cells (BMCMC) were used after 3–5 wk of culture (>98% mast cells by flow cytometry for c-Kit expression). Thrombin induced β-hexosaminidase, IL-6, and matrix metalloproteinase-9 release from BMCMC. Thrombin and the PAR-1-activating peptide AparafluoroFRCyclohexylACitY-NH2 (cit) induced BMCMC adhesion to FN in a dose-dependent fashion, while the PAR-1-inactive peptide FSLLRY-NH2 had no effect. Thrombin and cit induced also BMCMC adhesion to laminin. Thrombin-mediated adhesion to FN was inhibited by anti-α5 integrin Ab (51.1 ± 6.7%; n = 5). The combination of anti-α5 and anti-α4 Abs induced higher inhibition (65.7 ± 7.1%; n = 5). Unlike what is known for FcεRI-mediated adhesion, PAR-1-mediated adhesion to FN did not increase mediator release. We then explored the signaling pathways involved in PAR-1-mediated mast cell adhesion. Thrombin and cit induced p44/42 and p38 phosphorylation. Pertussis toxin inhibited PAR-1-mediated BMCMC adhesion by 57.3 ± 7.3% (n = 4), indicating that Gi proteins are involved. Wortmannin and calphostin almost completely inhibited PAR-1-mediated mast cell adhesion, indicating that PI-3 kinase and protein kinase C are involved. Adhesion was partially inhibited by the mitogen-activated protein kinase kinase 1/2 inhibitor U0126 (24.5 ± 3.3%; n = 3) and the p38 inhibitor SB203580 (25.1 ± 10.4%; n = 3). The two inhibitors had additive effects. Therefore, thrombin mediates mast cell adhesion through the activation of Gi proteins, phosphoinositol 3-kinase, protein kinase C, and mitogen-activated protein kinase pathways.

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Section: Discussionmentioning

confidence: 91%

Thrombin Induces Mast Cell Adhesion to Fibronectin: Evidence for Involvement of Protease-Activated Receptor-1

Vliagoftis

2002

The Journal of Immunology

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“…26 (ii) RANTES is one of the activation factors of Erk and p38 members of the mitogen-activated protein kinase (MAPK) family that are involved in regulating cell proliferation and differentiation. 17,25,27,28 Interestingly, p38 is considered to be a master switch between benign and destructive insulitis and therefore provokes the development of T1D. 29 Inhibition of p38 MAPK leads to the inhibition of Th1 immunity and prevents NOD mice from developing diabetes.…”

Section: Discussionmentioning

confidence: 99%

Genetic variants of RANTES are associated with serum RANTES level and protection for type 1 diabetes

et al. 2006

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RANTES (regulated on activation, normal T-cell expressed and secreted) is a T-helper type 1 (Th1) chemokine that promotes T-cell activation and proliferation. RANTES is genetically associated with asthma, sarcoidosis and multiple sclerosis. The concentration of RANTES is increased at inflammation sites in different autoimmune diseases. Type 1 diabetes (T1D) is a Th1-mediated disease with complex genetic predisposition. We tested RANTES as a candidate gene for association with T1D using three single-nucleotide polymorphism (SNP) variants (rs4251719, rs2306630 and rs2107538) to capture haplotype information. The minor alleles of all SNPs were transmitted less frequently to T1D offspring (transmission rates 37.3% (P ¼ 0.002), 38.7% (P ¼ 0.007) and 41.0% (P ¼ 0.01)) and were less frequently present in patients compared to controls (P ¼ 0.009, 0.03 and 0.04, respectively). A similar protective effect was observed for the haplotype carrying three minor alleles (transmission disequilibrium test (TDT): P ¼ 0.003; odds ratio (OR) ¼ 0.55; confidence interval (CI): 0.37-0.83; case/control: P ¼ 0.03; OR ¼ 0.74; CI: 0.55-0.98). Both patients and controls carrying the protective haplotype express significantly lower serum levels of RANTES compared to non-carriers. Subsequently, we tested a cohort of 310 celiac disease patients, but failed to detect association. RANTES SNPs are significantly associated with RANTES serum concentration and development of T1D. The rs4251719*A-rs2306630*A-rs2107538*A haplotype associated with low RANTES production confers protection from T1D. Our data imply that RANTES is associated with T1D both genetically and functionally, and contributes to diabetesprone Th1 cytokine profile.

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“…The p44/p42 MAPK pathway is a critical regulator of cell growth, migration, and differentiation (30,47). Several chemokines, including RANTES, are known to cause p44/p42 MAPK activation in various cell types (10,12,66). Signaling through GPCRs can activate the p44/p42 MAPKs through both G ␣i -dependent (Ptx-sensitive) and G ␣i -independent (Ptx-insensitive) mechanisms (45).…”

Section: Resultsmentioning

confidence: 99%

Interaction of the CC-Chemokine RANTES with Glycosaminoglycans Activates a p44/p42 Mitogen-Activated Protein Kinase-Dependent Signaling Pathway and Enhances Human Immunodeficiency Virus Type 1 Infectivity

Chang

Gordon

Roscic-Mrkic

et al. 2002

J Virol

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The interaction of the CC-chemokine RANTES with its cell surface receptors transduces multiple intracellular signals: low concentrations of RANTES (1 to 10 nM) stimulate G-protein-coupled receptor (GPCR) activity, and higher concentrations (1 M) activate a phosphotyrosine kinase (PTK)-dependent pathway. Here, we show that the higher RANTES concentrations induce rapid tyrosine phosphorylation of multiple proteins. Several src-family kinases (Fyn, Hck, Src) are activated, as is the focal adhesion kinase p125 FAK and, eventually, members of the p44/p42 mitogen-activated protein kinase (MAPK) family. This PTK signaling pathway can be activated independently of known seven-transmembrane GPCRs for RANTES because it occurs in cells that lack any such RANTES receptors. Instead, activation of the PTK signaling pathway is dependent on the expression of glycosaminoglycans (GAGs) on the cell surface, in that it could not be activated by RANTES in GAG-deficient cells. We have previously demonstrated that RANTES can both enhance and inhibit infection of cells with human immunodeficiency virus type 1 (HIV-1). Here we show that activation of both PTK and MAPK is involved in the enhancement of HIV-1 infectivity caused by RANTES in cells that lack GPCRs for RANTES but which express GAGs.

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Augmentation of RANTES-Induced Extracellular Signal-Regulated Kinase Mediated Signaling and T Cell Adhesion by Elastase-Treated Fibronectin

Cited by 17 publications

References 37 publications

Thrombin Induces Mast Cell Adhesion to Fibronectin: Evidence for Involvement of Protease-Activated Receptor-1

Thrombin Induces Mast Cell Adhesion to Fibronectin: Evidence for Involvement of Protease-Activated Receptor-1

Genetic variants of RANTES are associated with serum RANTES level and protection for type 1 diabetes

Interaction of the CC-Chemokine RANTES with Glycosaminoglycans Activates a p44/p42 Mitogen-Activated Protein Kinase-Dependent Signaling Pathway and Enhances Human Immunodeficiency Virus Type 1 Infectivity

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