Fischer, Christina and Weber-Steffens, Dorothea and Kreutz, Marina and Hehlgans, Thomas (2022) Propionate induces cross-tolerance to TLR1/2 and TLR4 agonists in an IFIT-dependent manner. IMMUNOBIOLOGY, 227 (2): 152186. ISSN 0171-2985, 1878-3279
Full text not available from this repository. (Request a copy)Abstract
In this study, we have identified Interferon-stimulated genes (ISGs), especially IFIT1, 2 and 3, as target genes of propionate-induced signalling in the human epithelial cell line A549, the monocytic cell line THP-1 as well as in primary, human peripheral blood-derived macrophages (PBMs). Induction of the IFIT gene family by propionate negatively regulates TLR-induced signalling. Propionate stimulation results in downregulation of proinflammatory cytokine and chemokine expression as well as MHC class II expression upon TLR1/2 and TLR4 re-stimulation in A549 and THP-1 cells as well as in PBMs, demonstrating that propionate-induced signalling is involved in the induction of TLR cross-tolerance. Signalling pathway analysis clearly demonstrates that propionate-induced IFIT expression is mediated by FFAR2 in a G alpha q/11 signalling pathway-dependent manner. Furthermore, propionate-induced IFIT expression is dependent on IFN type I and/or type III-mediated signalling since pre-treatment of A549 cells with Ruxolitinib, a specific JAK1/2 tyrosine kinase inhibitor, prior to stimulation with propionate, inhibited the upregulation of IFIT1 expression. The hypo-responsiveness towards TLR1/2 and TLR4 agonists seems to be mediated by different members of the IFIT gene family in a cell type-specific manner. Collectively, our data indicate that propionate-induced signalling controls pro-inflammatory responses by activation of IFN type I and/or type III-induced and IFIT-mediated counter-regulatory mechanisms in order to protect against exacerbating inflammatory reactions.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INTERFERON; RECEPTORS; PROTEIN; GENES; BETA; Immune regulation; Bacterial metabolites; Interferon-stimulated genes; IFITs; TLR tolerance |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Jan 2024 06:24 |
| Last Modified: | 29 Jan 2024 13:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/56977 |
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