Induction of vascular cell adhesion molecule-1 expression by IL-4 in human aortic smooth muscle cells is not associated with increased nuclear NF-?B levels

Wright, Paul S.; Cooper, Judith R.; Kropp, K; Busch, Steve

doi:10.1002/(sici)1097-4652(199909)180:3<381::aid-jcp9>3.0.co;2-f

Cited by 24 publications

(11 citation statements)

References 20 publications

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“…L eukocyte migration from the blood into tissues is vital for immune surveillance and inflammation (1)(2)(3)(4)(5). Recent studies on endothelial cell adhesion molecules indicate that lymphocyte binding triggers active endothelial cell signals that regulate leukocyte migration (6 -8).…”

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confidence: 91%

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VCAM-1 Activation of Endothelial Cell Protein Tyrosine Phosphatase 1B

Deem

Abdala‐Valencia

Cook‐Mills

2007

The Journal of Immunology

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Lymphocytes migrate from the blood into tissue by binding to and migrating across endothelial cells. One of the endothelial cell adhesion molecules that mediate lymphocyte binding is VCAM-1. We have reported that binding to VCAM-1 activates endothelial cell NADPH oxidase for the generation of reactive oxygen species (ROS). The ROS oxidize and stimulate an increase in protein kinase C (PKC)α activity. Furthermore, these signals are required for VCAM-1-dependent lymphocyte migration. In this report, we identify a role for protein tyrosine phosphatase 1B (PTP1B) in the VCAM-1 signaling pathway. In primary cultures of endothelial cells and endothelial cell lines, Ab cross-linking of VCAM-1 stimulated an increase in serine phosphorylation of PTP1B, the active form of PTP1B. Ab cross-linking of VCAM-1 also increased activity of PTP1B. This activation of PTP1B was downstream of NADPH oxidase and PKCα in the VCAM-1 signaling pathway as determined with pharmacological inhibitors and antisense approaches. In addition, during VCAM-1 signaling, ROS did not oxidize endothelial cell PTP1B. Instead PTP1B was activated by serine phosphorylation. Importantly, inhibition of PTP1B activity blocked VCAM-1-dependent lymphocyte migration across endothelial cells. In summary, VCAM-1 activates endothelial cell NADPH oxidase to generate ROS, resulting in oxidative activation of PKCα and then serine phosphorylation of PTP1B. This PTP1B activity is necessary for VCAM-1-dependent transendothelial lymphocyte migration. These data show, for the first time, a function for PTP1B in VCAM-1-dependent lymphocyte migration.

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supporting

confidence: 91%

“…VCAM-1 stimulates endothelial cell NADPH oxidase-catalyzed production of nontoxic levels of reactive oxygen species (ROS) 4 (1 M H 2 O 2 ) (9,12). In contrast, binding to VCAM-1 does not activate other ROS-generating enzymes in endothelial cells such as NO synthase (9).…”

mentioning

confidence: 99%

VCAM-1 Activation of Endothelial Cell Protein Tyrosine Phosphatase 1B

Deem

Abdala‐Valencia

Cook‐Mills

2007

The Journal of Immunology

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“…Moreover, IL-4 has been shown to induce VCAM-1 mRNA in VSMC (23,24). In the next set of experiments, we wished to determine whether thrombin induces VCAM-1 expression in VSMC.…”

Section: Thrombin Fails To Induce Vcam-1 Mrna Expression In Vascular mentioning

confidence: 94%

Thrombin Stimulation of Vascular Adhesion Molecule-1 in Endothelial Cells Is Mediated by Protein Kinase C (PKC)-δ-NF-κB and PKC-ζ-GATA Signaling Pathways

Minami

Abid

Zhang

et al. 2003

Journal of Biological Chemistry

106

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We recently demonstrated that thrombin induces the expression of vascular adhesion molecule-1 (VCAM-1) in endothelial cells by an NF-B-and GATA-dependent mechanism. In the present study, we describe the signaling pathways that mediate this response. Thrombin stimulation of the VCAM-1 gene and promoter in human umbilical vein endothelial cells was inhibited by preincubation with the phosphatidylinositol 3-kinase inhibitor, LY294002, the protein kinase C (PKC)-␦ inhibitor, rottlerin, a PKC-peptide inhibitor, or by overexpression of dominant negative (DN)-PKC-. In electrophoretic mobility shift assays, thrombin-mediated induction of NF-B p65 binding to two NF-B motifs in the upstream promoter region of VCAM-1 was blocked by LY294002 and rottlerin, whereas the inducible binding of GATA-2 to a tandem GATA motif was inhibited by LY294002 and the PKC-peptide inhibitor. In co-transfection assays, thrombin stimulation of a minimal promoter containing multimerized VCAM-1 NF-B sites was inhibited by DN-PKC-␦ but not DN-PKC-. In contrast, thrombin-mediated transactivation of a minimal promoter containing tandem VCAM-1 GATA motifs was inhibited by DN-PKC-but not DN-PKC-␦. Finally, thrombin failed to induce VCAM-1 expression in vascular smooth muscle cells. Taken together, these data suggest that the endothelial cell-specific effect of thrombin on VCAM-1 expression involves the coordinate activity of PKC-␦-NF-B and PKC--GATA signaling pathways. Vascular adhesion molecule-1 (VCAM-1)1 is a 110-kDa cell surface glycoprotein that is expressed in cytokine-activated endothelial cells (1). The VCAM-1 promoter, originally cloned and characterized in cultured endothelial cells (2), represents a potentially valuable tool for dissecting the molecular mechanisms of endothelial cell activation. Several studies have demonstrated the importance of two tandem NF-B elements located at position Ϫ77 and Ϫ63, relative to the transcriptional start site, in transducing the response to inflammatory mediators (2-4). Other studies have provided evidence for the role of co-stimulators in mediating cytokine response, including Sp1 (5), activating protein-1 (6), and interferon regulatory factor-1 (7).In a recent report, we showed that the incubation of endothelial cells with thrombin or the PAR-1 agonist, thrombin receptor activation peptide (TRAP), resulted in increased VCAM-1 mRNA levels and VCAM-1 promoter activity (8). Not surprisingly, a mutation of the tandem NF-B motif blocked the response to thrombin. Moreover, in electrophoretic mobility shift assays, thrombin induced the binding of p65 homodimers to the two adjacent NF-B sites in the VCAM-1 promoter. A more interesting finding was that a mutation of a tandem GATA motif (located at Ϫ244 and Ϫ259) also attenuated the thrombin response. Consistent with these results, thrombin treatment resulted in increased binding of GATA-2 to the VCAM-1 promoter. These data suggested that thrombin-mediated induction of VCAM-1 involves the coordinate activity of NF-B p65 and GATA-2 and raised new questions as to...

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“…IL-1 ␤ and TNF ␣ stimulate the NF-B-dependent expression of the cell adhesion molecules ICAM-1 and VCAM-1 resulting in enhanced adhesion between SMCs and monocytes [53][54][55] . In contrast, IL-4 induces VCAM expression through an NF-B-independent pathway [56] , suggesting that alternative inflammatory signaling pathways can stimulate cell adhesion molecule expression. The interaction between monocytes and SMCs is sufficient to stimulate the expression of IL-6 and MCP-1 [57] , suggesting that cell adhesion molecule expression in the SMC layer may propagate the local inflammatory response.…”

Section: Inflammation Begets Inflammation: the Smc Inflammatory Respomentioning

confidence: 99%

Complex Regulation and Function of the Inflammatory Smooth Muscle Cell Phenotype in Atherosclerosis

et al. 2009

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Induction of vascular cell adhesion molecule-1 expression by IL-4 in human aortic smooth muscle cells is not associated with increased nuclear NF-?B levels

Cited by 24 publications

References 20 publications

VCAM-1 Activation of Endothelial Cell Protein Tyrosine Phosphatase 1B

VCAM-1 Activation of Endothelial Cell Protein Tyrosine Phosphatase 1B

Thrombin Stimulation of Vascular Adhesion Molecule-1 in Endothelial Cells Is Mediated by Protein Kinase C (PKC)-δ-NF-κB and PKC-ζ-GATA Signaling Pathways

Complex Regulation and Function of the Inflammatory Smooth Muscle Cell Phenotype in Atherosclerosis

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