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Interleukin-13 selectively induces monocyte chemoattractant protein-1 synthesis and secretion by human endothelial cells. Involvement of IL-4R alpha and Stat6 phosphorylation.
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.[1]References
- Interleukin-13 selectively induces monocyte chemoattractant protein-1 synthesis and secretion by human endothelial cells. Involvement of IL-4R alpha and Stat6 phosphorylation. Goebeler, M., Schnarr, B., Toksoy, A., Kunz, M., Bröcker, E.B., Duschl, A., Gillitzer, R. Immunology (1997) [Pubmed]
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