IL-10 regulates BCL-3 mediated adaptation to repeated TLR4 stimulation in macrophages

---

Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B708
Abstract ID: 5739

Presenting Author:
Hannes Bongartz , Postdoctoral fellow at NIAID, NIH

Abstract:

Due to its potential to initiate pathological inflammation, Toll-like receptor 4 (TLR4) mediated activation of macrophages has been studied intensely, revealing a multitude of regulatory components and mechanisms. Systematically varying dose and duration of priming and re-exposure of bone marrow derived macrophages (BMDM) to the TLR4 ligand KLA, we quantified dose-dependent adaptation and sensitization at multiple stages of the signaling response, including TLR4 internalization, MAPK activation, and nuclear translocation of transcription factors. We find that the anti-inflammatory cytokine IL-10 neither interferes with MyD88-dependent MAPK, NFkB nor TRIF-dependent IRF signaling upon restimulation after priming. Instead, IL-10 is found to affect nuclear translocation of the transcriptional regulator BCL-3 while showing a surprisingly strong dependence on the KLA exposure history. Moreover, chromatin immunoprecipitation of BCL-3 reveals that BCL-3 occupies kb sites in the TNFa and IL-6 genes in hypo-responsive macrophages in an IL-10 dependent manner.

This work was supported by the intramural program of the NIAID, NIH.