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Reverse Signaling through Membrane-bound Interleukin-15
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-γ-activated human monocytes in reverse signaling upon stimulation with soluble IL-15 receptor-α or anti-IL-15 antibodies, m...
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Published in: | The Journal of biological chemistry 2004-10, Vol.279 (40), p.42192-42201 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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-γ-activated human monocytes in reverse signaling upon stimulation with
soluble IL-15 receptor-α 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-α, 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. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M403182200 |