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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.01766

The NADPH Oxidase Nox4 controls polarization of macrophages in a NFκB-dependent manner.

 Katrin Schröder1*,  Valeska Helfinger1, Katalin Palfi1 and Andreas Weigert1
  • 1University Hospital Frankfurt, Germany

The family of NADPH oxidases represents a source of reactive oxygen species (ROS). Within this family, Nox4 is special, as it constitutively produces H2O2. The loss of Nox4 promotes inflammation. A major cellular component of inflammation is the macrophage population, which divides in several subpopulations with pro-inflammatory M1 and wound-healing M2 macrophages being extremes of the functional spectrum of these cells. As controversial findings on Nox4 expression in macrophages exist, we hypothesize that Nox4 expression is only present in a subpopulation of macrophages, where it may determine the phenotype. In a murine inflammation-driven fibro sarcoma model Nox4-deficiency results an increase in the expression of pro-inflammatory genes and cytokines and higher amounts of pro-inflammatory Ly6C+ macrophages in the tumors. Ex vivo, bone marrow-derived macrophages deficient in Nox4 displayed a reduced M2 polarization whereas M1 markers were elevated. ROS levels where augmented in Nox4-/- cells polarized to M1 accompanied by a higher expression of Nox2. Mechanistically, Nox4-deficiency reduces STAT6 activation and promotes NFκB activity, with the latter being responsible for the higher level of Nox2 in Nox4-deficient M1-polarized macrophages.
Collectively the data obtained in this study propose an anti-inflammatory role of Nox4 in macrophages. This is achieved by an enhanced M2 polarization and a suppression of NFκB activity.

Keywords: NADPH oxidase, Nox4, Macrophages, polarization, reactive oxygen species, NADPH Oxidase, NOX4, reactive oxygen species, Macropahge, polarization

Received: 12 Aug 2018; Accepted: 11 Jul 2019.

Edited by:

Claudia Monaco, University of Oxford, United Kingdom

Reviewed by:

Gabor Csanyi, Medical College of Georgia, Augusta University, United States
Fernando O. Martinez, University of Surrey, United Kingdom  

Copyright: © 2019 Schröder, Helfinger, Palfi and Weigert. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Katrin Schröder, University Hospital Frankfurt, Frankfurt, Germany, schroeder@vrc.uni-frankfurt.de