Reverse signaling through membrane-bound interleukin-15
| Autor: | Vadim Budagian, Robert H. Silverman, Silvia Bulfone-Paus, Zane Orinska, Elena Bulanova, Thomas Pohl, Ernest C. Borden |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Receptor complex medicine.medical_treatment Biology Ligands Biochemistry Monocytes Focal adhesion Interferon-gamma Cell Movement Cell Line Tumor LNCaP medicine Humans Molecular Biology Cells Cultured Interleukin-15 Immunity Cellular Receptors Interleukin-15 Interleukin Membrane Proteins Prostatic Neoplasms Receptors Interleukin-2 Cell Biology Protein-Tyrosine Kinases Cell biology Cytokine Interleukin 15 Cell culture Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Immunology Cytokines Additions and Corrections Signal transduction Mitogen-Activated Protein Kinases Signal Transduction |
| Popis: | The results from this study implicate membrane-anchored interleukin (IL)-15 constitutively expressed on the cell surface of PC-3 human prostate carcinoma cells and interferon-gamma-activated human monocytes in reverse signaling upon stimulation with soluble IL-15 receptor-alpha or anti-IL-15 antibodies, mediating the outside-to-inside signal transduction that involves the activation of members of the MAPK family (ERK and p38) and focal adhesion kinase. The presence of membrane-bound IL-15 was not dependent on the expression of the trimeric IL-15 receptor complex by these cells and resisted treatment with acidic buffer or trypsin. Reverse signaling through membrane-bound IL-15 considerably increased the production of several pro-inflammatory cytokines by monocytes, such as IL-6, IL-8, and tumor necrosis factor-alpha, thereby indicating the relevance of this process to the complex immunomodulatory function of these cells. Furthermore, stimulation of transmembrane IL-15 also enhanced the transcription of IL-6 and IL-8 in the PC-3 cell line and promoted migration of PC-3 cells as well as LNCaP human prostate carcinoma cells stably expressing IL-15 on the cell surface. Thus, IL-15 can exist as a biologically active transmembrane molecule that possesses dual ligand-receptor qualities with a potential to induce bidirectional signaling. This fact highlights a new level of complexity in the biology of IL-15 and offers novel important insights into our understanding of the cellular responses modulated by this pleiotropic cytokine. |
| Databáze: | OpenAIRE |
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