Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA024

Poster Communications

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

V. Helfinger1, K. Palfi1, A. Weigert2, K. Schröder1

1. Institute for Cardiovascular Physiology, Goethe University Frankfurt, Frankfurt am Main, Germany. 2. Institute for Biochemistry I, Frankfurt am Main, 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 this functional spectrum of 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 fibrosarcoma 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 NFKB 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 NFKB activity.

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