Interleukin-6 is a direct mediator of T cell migration.
Interleukin (IL)-6 is a pleiotropic cytokine involved in the differentiation and proliferation of hematopoietic cells. Hepatocytes respond to IL-6 with the synthesis and secretion of acute-phase proteins. In addition, IL-6 plays a role as a migration factor in vivo. In the present paper, we studied the potential of IL-6 to mediate migration of human primary T cells and T cell-derived cell lines. IL-6 was found to induce migration only in the presence of extracellular matrix, suggesting a cross-talk between the IL-6- and integrin signal transduction pathways. Furthermore, an IL-6 gradient is required for chemotactic migration. This activity is not due to the release of secondary chemotactic activities, but is a direct response to IL-6. T cell migration could also be observed in response to IL-11, but no migration was found after stimulation with leukemia inhibitory factor or oncostatin M, although these cytokines signal through gp130-containing receptor complexes. Finally, we present evidence that activation of the mitogen-activated protein kinase (MAPK) cascade, the phosphatidylinositol 3-kinase as well as the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is crucial for IL-6-induced migration. Selective activation of the JAK/STAT or the MAPK cascade by mutated receptor proteins shows a crucial role of IL-6-initiated SH2 domain-containing tyrosine phosphatase 2/MAPK activity for migration.
Weissenbach
Manuela
M
Department of Biochemistry, RWTH Aachen, Aachen, Germany.
Clahsen
Thomas
T
Weber
Christian
C
Spitzer
Dirk
D
Wirth
Dagmar
D
Vestweber
Dietmar
D
Heinrich
Peter C
PC
Schaper
Fred
F
D002460:Cell Line; D002465:Cell Movement / Q000276:immunology*; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000276:immunology / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D016023:Integrins / Q000276:immunology / Q000378:metabolism; D017370:Interleukin-11 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D016023:Integrins; D017370:Interleukin-11; D015850:Interleukin-6; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases