Authors:	Müller-Calleja, Nadine Hollerbach, Anne Canisius, Antje Orning, Carolin Strand, Susanne Lackner, Karl J.
Title:	Rapid translocation of intracellular toll-like receptors depends on endosomal NADPH oxidase
Online publication date:	11-Sep-2023
Year of first publication:	2023
Language:	english
Abstract:	Endosomal toll-like receptors (TLRs) must be translocated from the endoplasmic reticulum (ER) to the endosome and proteolytically cleaved within the endosome before they can induce cellular signals. As ligands for these TLRs are also liberated from apoptotic or necrotic cells, this process is controlled by several mechanisms which shall ensure that there is no inadvertent activation. We have shown previously that antiphospholipid antibodies induce endosomal NADPH-oxidase (NOX) followed by the translocation of TLR7/8 to the endosome. We show now that endosomal NOX is required for the rapid translocation of TLR3, TLR7/8, and TLR9. Deficiency of gp91phox, the catalytic subunit of NOX2, or inhibition of endosomal NOX by the chloride channel blocker niflumic acid both prevent immediate (i.e., within 30 min) translocation of these TLRs as shown by confocal laser scanning microscopy. Under these conditions, the induction of mRNA synthesis for TNF-α and secretion of TNF-α is delayed by approx. 6–9 h. However, maximal expression of TNF-α mRNA or secretion of TNF-α is not significantly reduced. In conclusion, these data add NOX2 as another component involved in the orchestration of cellular responses to ligands of endosomal TLRs.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-9517
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY-NC-ND
Information on rights of use:	https://creativecommons.org/licenses/by-nc-nd/4.0/
Journal:	European journal of immunology 53 9
Pages or article number:	2250271
Publisher:	Wiley-VCH
Publisher place:	Weinheim
Issue date:	2023
ISSN:	1521-4141
Publisher DOI:	10.1002/eji.202250271
Appears in collections:	DFG-491381577-H