Beta-defensins activate macrophages and synergize in pro-inflammatory cytokine expression induced by TLR ligands

Barabas, Nicola and Roehrl, Johann and Holler, Ernst and Hehlgans, Thomas (2013) Beta-defensins activate macrophages and synergize in pro-inflammatory cytokine expression induced by TLR ligands. IMMUNOBIOLOGY, 218 (7). pp. 1005-1011. ISSN 0171-2985,

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Abstract

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 G(i)-protein-coupled receptor signaling provide evidence that this effect seems to be mediated by a G(i)-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 beta-defensins activate primary macrophages and enhance pro-inflammatory responses by using G(i)PCRs in order to support inflammatory reactions induced by TLR ligands. (c) 2012 Elsevier GmbH. All rights reserved.

Item Type: Article
Uncontrolled Keywords: DENDRITIC CELLS; RECEPTOR; CATHELICIDIN; MONOCYTES; IMMATURE; IMMUNITY; INNATE; LL-37; Beta-defensin; G protein-coupled receptors; Pro-inflammatory cytokines; TLR agonists
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Immunologie
Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 07 Apr 2020 09:56
Last Modified: 07 Apr 2020 09:56
URI: https://pred.uni-regensburg.de/id/eprint/16470

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