Sodium channel γENaC mediates IL-17 synergized high salt induced inflammatory stress in breast cancer cells

Chronic inflammation is known to play a critical role in the development of cancer. Recent evidence suggests that high salt in the tissue microenvironment induces chronic inflammatory milieu. In this report, using three breast cancer-related cell lines, we determined the molecular basis of the potential synergistic inflammatory effect of sodium chloride (NaCl) with interleukin-17 (IL-17). Combined treatment of high NaCl (0.15 M) with sub-effective IL-17 (0.1 nM) induced enhanced growth in breast cancer cells along with activation of reactive nitrogen and oxygen (RNS/ROS) species known to promote cancer. Similar effect was not observed with equi-molar mannitol. This enhanced of ROS/RNS activity correlates with upregulation of gamma ENaC an inflammatory sodium channel. The similar culture conditions have also induced expression of pro-inflammatory cytokines such as IL-6, TNF alpha etc. Taken together, these data suggest that high NaCl in the cellular microenvironment induces a gamma ENaC mediated chronic inflammatory response with a potential pro-carcinogenic effect. (C) 2015 Elsevier Inc. All rights reserved.