IL‐4 and IL‐13 exhibit comparable abilities to reduce pyrogen‐induced expression of procoagulant activity in endothelial cells and monocytes

Herbert, Jean‐Marc; Savi, Pierre; Laplace, Marie-Claude; Lalé, Alain; Dol, Frédérique; Dumas, A.; Labit, C.; Minty, Adrian

doi:10.1016/0014-5793(93)80941-m

Cited by 75 publications

(41 citation statements)

References 16 publications

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“…DNase activity was destroyed by heating for 10 min at 65 Њ C in the presence of 2 mM EDTA. For cDNA synthesis mRNA (2 g) was incubated with oligo(dT) [12][13][14][15][16][17][18] (10 g/ml) at 70 Њ C for 10 min and then rapidly cooled on ice. RT was carried out in a buffer containing 50 mM Tris-HCl (pH 8.3), 75 mM KCl, 10 mM DTT, 3 mM MgCl 2 , 0.5 mM each dATP, dCTP, dGTP, and dTTP in the presence or absence of 200 U Superscript II reverse transcriptase (GIBCO-BRL) in a total volume of 50 l. cDNA synthesis was performed at 43 Њ C for 1 h and the reaction was terminated by heating at 90 Њ C for 5 min.…”

Section: Methodsmentioning

confidence: 99%

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IL-4 and IL-13 activate the JAK2 tyrosine kinase and Stat6 in cultured human vascular endothelial cells through a common pathway that does not involve the gamma c chain.

Palmer-Crocker

Hughes²,

Pober³

1996

J. Clin. Invest.

101

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1 and markedly augments VCAM-1 expression induced by TNF or IL-1 (1-6). These changes favor the binding of eosinophils and T cells to endothelial cells (ECs). In addition, IL-4-treated ECs secrete the chemokine MCP-1 (7) and selectively stimulate transendothelial migration of eosinophils in vitro (8). The effects of IL-4 on EC differ from those on hematopoietic cell types in that IL-4 is not an endothelial mitogen or survival factor.IL-13 is another pleiotropic immunoregulatory cytokine (9, 10) that shares a number of biological properties with IL-4 (11-16). IL-13, like IL-4, selectively induces VCAM-1 in cultured human ECs (17, 18). IL-13 has been shown recently to stimulate tyrosine phosphorylation of the IL-4-binding subunit of the 140-kD IL-4 receptor (IL-4R) in a number of hematopoietic cell types (19), suggesting that IL-4 and IL-13 may activate a common tyrosine kinase. Two recent findings further suggest that the IL-13-binding subunit of the IL-13 receptor (IL-13R) may share at least one subunit with the IL-4R: ( a ) the IL-4 mutant protein Y124D, which inhibits IL-4-dependent reactions (20) also inhibits effects of IL-13 (21, 22); and ( b ) IL-13 competes with radiolabeled IL-4 for binding to some cells (21-24).The IL-2 receptor (IL-2R) ␥ chain is a functional component of the IL-4R in lymphocytes, required for tyrosine phosphorylation of the insulin receptor substrate-1 in response to IL-4 (25) and for IL-4-induced cell proliferation (26). The (IL-2R) ␥ chain, recently renamed the common ␥ chain ( ␥ c chain), is also a common receptor component of many other members of the cytokine receptor superfamily including , [30][31][32]34). It is not known if IL-13 can signal through ␥ c , but some cell lines of hematopoietic origin are known to respond to IL-4 and IL-13 in the absence of ␥ c (24,35). This evidence suggests two distinct signaling pathways for IL-4, one involving ␥ c , and an alternate pathway, shared with IL-13, that does not use ␥ c .Previous work by our laboratory has shown that IL-4 activates a protein tyrosine kinase that phosphorylates the IL-4R binding subunit in cultured human ECs and that activation of this protein tyrosine kinase may play a part in the signaling pathway leading to increased VCAM-1 expression in response to . We now show that IL-13, like IL-4, causes the activation of a protein tyrosine kinase in ECs that phosphorylates IL-4R, that both cytokines activate JAK2 and the Stat6 transcription factor, and that these responses cannot involve ␥ c , since this protein is not expressed in ECs. MethodsCell isolation and culture. ECs were isolated and cultured as described previously (37,38). ECs used in these experiments were of passage levels 2 to 5 and were free of detectable CD45 ϩ leukocytes. PHA- 1. Abbreviations used in this paper: EC, endothelial cell; JAK, Janus kinase; RT, reverse transcription; Stat, signal transducer and activator of transcription; VCAM-1, vascular cell adhesion molecule-1.

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Section: Methodsmentioning

confidence: 99%

“…IL-13 is another pleiotropic immunoregulatory cytokine (9,10) that shares a number of biological properties with IL-4 (11)(12)(13)(14)(15)(16). IL-13, like IL-4, selectively induces VCAM-1 in cultured human ECs (17,18).…”

Section: Introductionmentioning

confidence: 99%

IL-4 and IL-13 activate the JAK2 tyrosine kinase and Stat6 in cultured human vascular endothelial cells through a common pathway that does not involve the gamma c chain.

Palmer-Crocker

Hughes²,

Pober³

1996

J. Clin. Invest.

101

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“…In particular, vascular endothelial cells respond to IL-4. In endothelial cells, IL-4 induces or modulates the expression of urokinase-type plasminogen activator (13), monocyte chemotactic protein-1 (14), IL-6 (15), VCAM-1 (16), eotaxin (17), thrombomodulin (18), and RANTES (19). These actions of IL-4 on endothelium are likely to contribute to the pathophysiology of asthma and atopic inflammation (20).…”

Section: Nonhematopoietic Expression Of Janus Kinase 3 Is Required Fomentioning

confidence: 99%

Nonhematopoietic Expression of Janus Kinase 3 Is Required for Efficient Recruitment of Th2 Lymphocytes and Eosinophils in OVA-Induced Airway Inflammation

Verbsky

Randolph

Shornick

et al. 2002

The Journal of Immunology

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Tyrosine kinases of the Janus kinase (Jak) family transduce signals from the type I and type II cytokine receptors. Jak3 is unique in this family because its expression must be induced and is predominantly limited to cells of the lymphoid and myeloid lineages. Deficient expression of Jak3 interferes with normal development and function of T, B, and NK cells. Using irradiated Jak3-deficient (Jak3−/−) mice reconstituted with normal bone marrow (Jak3−/− chimeric mice), we have investigated possible actions of Jak3 outside of the hematopoietic system. We show that efficient recruitment of inflammatory cells to the airways of OVA-sensitized mice challenged with aerosolized OVA requires the expression of Jak3 in radioresistant nonhematopoietic cells. Failure to develop eosinophil-predominant airway inflammation in Jak3−/− chimeric mice is not due to failure of T cell sensitization, because Jak3−/− chimeric mice showed delayed-type hypersensitivity responses indistinguishable from wild-type chimeric mice. Jak3−/− chimeric mice, however, express less endothelial-associated VCAM-1 after airway Ag challenge. Given the key role of VCAM-1 in recruitment of Th2 cells and eosinophils, our data suggest that Jak3 in airway-associated endothelial cells is required for the expression of eosinophilic airway inflammation. This requirement for nonhematopoietic expression of Jak3 represents the first demonstration of a physiological function of Jak3 outside of the lymphoid lineages.

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“…B, the membrane in panel A was then stripped and reprobed with Jak3 antisera. of thrombomodulin expression induced by TNF-␣, IL-1␤, and LPS in endothelium (24,25). IL-6 and monocyte chemotactic protein-1 are expressed in endothelium in response to IL-4 (16,17).…”

Section: Figmentioning

confidence: 99%

Expression of Janus Kinase 3 in Human Endothelial and Other Non-lymphoid and Non-myeloid Cells

Verbsky

Bach

Fang

et al. 1996

Journal of Biological Chemistry

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Members of the Janus kinase (Jak) family of protein tyrosine kinases have recently been implicated in the proximal signal transduction events of cytokine receptors. Jak3, a newly discovered member of this family, is believed to be normally limited in its expression to cells of the lymphoid and myeloid lineages. Herein we show that Jak3 is expressed in primary human vascular cells, as well as other non-lymphoid and non-myeloid cell types. Reverse transcriptase-polymerase chain reaction and Northern blot analysis revealed that Jak3 mRNA was expressed at low levels in human umbilical vein endothelial cells (HUVEC), human aortic smooth muscle cells (HASMC), A549 (human lung carcinoma), and DLD-1 (human colon adenocarcinoma) cells. Higher basal levels of Jak3 mRNA were detected in HMEC-1 (human microvascular cell line) and HepG2 (human hepatocellular carcinoma) cells. Jak3 mRNA expression was induced in HUVEC, HMEC-1, and HASMC by treatment with interleukin-1␤, tumor necrosis factor-␣, interferon-␥, and lipopolysaccharide. Jak3 protein was detectable at low levels in untreated HMEC-1, and these levels increased significantly with cytokine treatment. Furthermore, Jak3 protein was phosphorylated upon treatment of these cells with interleukin-4. This work shows that Jak3 is expressed or inducible in human vascular endothelial, vascular smooth muscle, and other nonlymphoid and non-myeloid cells, suggesting a broader role for Jak3 in the cytokine signal transduction of these cells.

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IL‐4 and IL‐13 exhibit comparable abilities to reduce pyrogen‐induced expression of procoagulant activity in endothelial cells and monocytes

Cited by 75 publications

References 16 publications

IL-4 and IL-13 activate the JAK2 tyrosine kinase and Stat6 in cultured human vascular endothelial cells through a common pathway that does not involve the gamma c chain.

IL-4 and IL-13 activate the JAK2 tyrosine kinase and Stat6 in cultured human vascular endothelial cells through a common pathway that does not involve the gamma c chain.

Nonhematopoietic Expression of Janus Kinase 3 Is Required for Efficient Recruitment of Th2 Lymphocytes and Eosinophils in OVA-Induced Airway Inflammation

Expression of Janus Kinase 3 in Human Endothelial and Other Non-lymphoid and Non-myeloid Cells

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