Universität zu Köln

Herb, Marc ORCID: 0000-0002-7533-0288, Gluschko, Alexander, Wiegmann, Katja, Farid, Alina, Wolf, Anne ORCID: 0000-0003-2551-9821, Utermoehlen, Olaf, Krut, Oleg, Kroenke, Martin and Schramm, Michael ORCID: 0000-0003-0226-9129 (2019). Mitochondrial reactive oxygen species enable proinflammatory signaling through disulfide linkage of NEMO. Sci. Signal., 12 (568). WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 1937-9145

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Abstract

A major function of macrophages during infection is initiation of the proinflammatory response, leading to the secretion of cytokines that help to orchestrate the immune response. Here, we identify reactive oxygen species (ROS) as crucial mediators of proinflammatory signaling leading to cytokine secretion in Listeria monocytogenes-infected macrophages. ROS produced by NADPH oxidases (Noxes), such as Nox2, are key components of the macrophage response to invading pathogens; however, our data show that the ROS that mediated proinflammatory signaling were produced by mitochondria (mtROS). We identified the inhibitor of kappa B (I kappa B) kinase (IKK) complex regulatory subunit NEMO [nuclear factor kappa B (NF-kappa B) essential modulator] as a target for mtROS. Specifically, mtROS induced intermolecular covalent linkage of NEMO through disulfide bonds formed by Cys(54) and Cys(347), which was essential for activation of the IKK complex and subsequent signaling through the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and NF-kappa B pathways that eventually led to the secretion of proinflammatory cytokines. We thus identify mtROS-dependent disulfide linkage of NEMO as an essential regulatory step of the proinflammatory response of macrophages to bacterial infection.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Herb, Marc UNSPECIFIED orcid.org/0000-0002-7533-0288 UNSPECIFIED Gluschko, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiegmann, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Farid, Alina UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Anne UNSPECIFIED orcid.org/0000-0003-2551-9821 UNSPECIFIED Utermoehlen, Olaf UNSPECIFIED UNSPECIFIED UNSPECIFIED Krut, Oleg UNSPECIFIED UNSPECIFIED UNSPECIFIED Kroenke, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Schramm, Michael UNSPECIFIED orcid.org/0000-0003-0226-9129 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-156707
DOI:	10.1126/scisignal.aar5926
Journal or Publication Title:	Sci. Signal.
Volume:	12
Number:	568
Date:	2019
Publisher:	AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication:	WASHINGTON
ISSN:	1937-9145
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TUMOR-NECROSIS-FACTOR; TOLL-LIKE RECEPTORS; KAPPA-B ACTIVATION; HYDROGEN-PEROXIDE; IMMUNE-RESPONSES; OXIDATIVE STRESS; LISTERIA; TNF; INNATE; GENE Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15670