Interleukin-13 selectively induces monocyte chemoattractant protein-1 synthesis and secretion by human endothelial cells. Involvement of IL-4R alpha and Stat6 phosphorylation - PubMed (original) (raw)

Interleukin-13 selectively induces monocyte chemoattractant protein-1 synthesis and secretion by human endothelial cells. Involvement of IL-4R alpha and Stat6 phosphorylation

M Goebeler et al. Immunology. 1997 Jul.

Abstract

Chemokines secreted by endothelium have been demonstrated to promote leucocyte recruitment to sites of inflammation. In the present study we investigated the effect of the T lymphocyte-secreted cytokine interleukin (IL)-13 on endothelial expression of chemokines. Employing in situ hybridization and enzyme-linked immunosorbent assay (ELISA) techniques we demonstrate that IL-13, which shares many of its activities with IL-4, selectively induces expression of the C-C chemokine monocyte chemoattractant protein (MCP)-1 in human umbilical vein endothelial cells (HUVEC). However, it fails to up-regulate other C-C and C-X-C chemokines potentially inducible in endothelium such as RANTES (regulated on activation, normal T expressed and secreted), gro-alpha, or IL-8. IL-13 dose-dependently induces monocyte chemotactic activity by HUVEC which can be efficiently blocked by neutralizing antisera against MCP-1. In contrast to the synergistic effect of IL-13 and tumour necrosis factor-alpha (TNF-alpha) on endothelial vascular cell adhesion molecule-1 (VCAM-1) surface expression, TNF-alpha-induced secretion of MCP-1 is not augmented by IL-13. Studying the signalling pathway activated by IL-13 it is demonstrated that a neutralizing monoclonal antibody (mAb) to the 140,000 MW component of the IL-4 receptor (IL-4R alpha) inhibits the effect of IL-13. Immunoprecipitation studies reveal that endothelial IL-4R alpha is rapidly tyrosine phosphorylated upon treatment with IL-13 and IL-4. We furthermore show that both cytokines activate the signal transducer and activator of transcription (Stat) protein-6 in endothelial cells. Our data suggest that IL-13 partly utilizes components of the IL-4 receptor signalling pathway for induction of endothelial MCP-1 expression to facilitate recruitment of blood leucocytes.

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