Inflammation and an influx of macrophages are common elements in many diseases.
Among pro-inflammatory cytokines, tumor necrosis factor (TNF) plays a central role by amplifying
the cytokine network. Progranulin (PGRN) is a growth factor that binds to TNF receptors and interferes
with TNF-mediated signaling. Extracellular PGRN is processed into granulins by proteases released
from immune cells. PGRN exerts anti-inflammatory effects, whereas granulins are pro-inflammatory.
The factors coordinating these ambivalent functions remain unclear. In our study, we identify Y-box
binding protein-1 (YB-1) as a candidate for this immune-modulating activity. Using a yeast-2-hybrid
assay with YB-1 protein as bait, clones encoding for progranulin were selected using stringent criteria
for strong interaction. We demonstrate that at physiological concentrations, YB-1 interferes with
the binding of TNF to its receptors in a dose-dependent manner using a flow cytometry-based
binding assay. We show that YB-1 in combination with progranulin interferes with TNF-mediated
signaling, supporting the functionality with an NF-B luciferase reporter assay. Together, we show
that YB-1 displays immunomodulating functions by affecting the binding of TNF to its receptors
and influencing TNF-mediated signaling via its interaction with progranulin.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89638 |
| Date | 09 February 2024 |
| Creators | Hessmann, Christopher L., Hildebrandt, Josephine, Shah, Aneri, Brandt, Sabine, Bock, Antonia, Frye, Björn C., Raffetseder, Ute, Geffers, Robert, Brunner-Weinzierl, Monika C., Isermann, Berend, Mertens, Peter R., Lindquist, Jonathan A. |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 7076 |
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