Wanke, Daniela and Mauch-Mucke, Katrin and Holler, Ernst and Hehlgans, Thomas (2016) Human beta-defensin-2 and-3 enhance pro-inflammatory cytokine expression induced by TLR ligands via ATP-release in a P2X7R dependent manner. IMMUNOBIOLOGY, 221 (11). pp. 1259-1265. ISSN 0171-2985,
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Our previous results indicate that HBD2 and HBD3 are chemotactic for a broad spectrum of leukocytes in a CCR6- and CCR2-dependent manner. In this study we report that pre-stimulation of primary human macrophages or THP-1 cells with HBD2 or HBD3 results in a synergistic, enhanced expression of pro-inflammatory cytokines and chemokines induced by TLR ligand re-stimulation. Experiments using specific inhibitors of the ATP-gated channel receptor P2X7 or its functional ligand ATP, suggest that the enhanced expression of pro-inflammatory cytokines and chemokines seems to be mediated by P2X7R. Furthermore, our data provide evidence that beta-defensins do not directly interact with P2X7R but rather induce the release of intracellular ATP. Interference with ATP release abrogated the synergistic effect mediated by HBD2 and HBD3 pre-stimulation in THP-1 cells. However, extracellular ATP alone seems not to be sufficient to elicit the enhanced synergistic effect on cytokine and chemokine expression observed by pre-stimulation of primary human macrophages or THP-1 cells with HBD2 or HBD3. Collectively, our findings provide new insights into the molecular mechanisms how HBD2 and HBD3 interact with cells of myeloid origin and demonstrate their immuno-modulating functions during innate immune responses. (C) 2016 Elsevier GmbH. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ANTIMICROBIAL PEPTIDES; BETA-DEFENSINS; IL-1-BETA; CELLS; MACROPHAGES; CHEMOTAXIS; STATES; Beta-defensins; p2x7 receptor; Pro-inflammatory cytokines; TLR agonists |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Apr 2019 12:53 |
| Last Modified: | 12 Apr 2019 12:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4073 |
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