Beta-defensins activate macrophages and synergize in pro-inflammatory cytokine expression induced by TLR ligands
| Autor: | Johann Röhrl, Thomas Hehlgans, Nicola Barabas, Ernst Holler |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Lipopolysaccharides
Receptors CCR6 CCR2 Chemokine beta-Defensins Receptors CCR2 Immunology Primary Cell Culture C-C chemokine receptor type 6 Chemokine receptor Mice Immunology and Allergy Animals CCL15 Phosphorylation Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 biology Chemistry Macrophages hemic and immune systems Drug Synergism Hematology Macrophage Activation Recombinant Proteins Cell biology Toll-Like Receptor 4 CXCL2 Gene Expression Regulation biology.protein B7-1 Antigen Cytokines Female B7-2 Antigen CCL25 CCL22 Signal Transduction |
| Zdroj: | Immunobiology. 218(7) |
| ISSN: | 1878-3279 |
| Popis: | Our previous studies indicated that mouse beta defensin 14 (mBD14, Defb14), a newly identified member of the beta-defensin super family, interacts with the chemokine receptors CCR2 and CCR6. In this study we report that pre-stimulation of primary mouse macrophages with mBD14 results in a synergistic, enhanced expression of pro-inflammatory cytokines and chemokines induced by TLR ligand re-stimulation. Experiments using specific inhibitors of Gi-protein-coupled receptor signaling provide evidence that this effect seems to be mediated by a Gi-protein-coupled receptor expressed on bone marrow derived macrophages. However, using primary macrophages derived from CCR6- and CCR2-deficient mice clearly demonstrated that the enhanced pro-inflammatory cytokine and chemokine expression is independent of the chemokine receptors CCR6 and CCR2. Additionally, signaling pathway analysis indicated that mBD14 is capable of inducing MAPK ERK1/2 phosphorylation and the induction of CD86 and F4/80 expression in bone marrow-derived macrophages after mBD14 stimulation. Collectively, our data indicate that β-defensins activate primary macrophages and enhance pro-inflammatory responses by using GiPCRs in order to support inflammatory reactions induced by TLR ligands. |
| Databáze: | OpenAIRE |
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