title: Sodium channel γENaC mediates IL-17 synergized high salt induced inflammatory stress in breast cancer cells.
abstract: 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 (0.15M) 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 γENaC an inflammatory sodium channel. The similar culture conditions have also induced expression of pro-inflammatory cytokines such as IL-6, TNFα etc. Taken together, these data suggest that high NaCl in the cellular microenvironment induces a γENaC mediated chronic inflammatory response with a potential pro-carcinogenic effect.
authors.affiliation: Department of Medicine, Mercy Hospital, St Louis, MO, USA.
authors.forename: Suneetha
authors.initials: S
authors.lastname: Amara
authors.affiliation: Department of Biological Sciences, Tennessee State University, Nashville, TN, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Ivy
authors.affiliation: Department of Biological Sciences, Tennessee State University, Nashville, TN, USA.
authors.forename: Elbert L
authors.initials: EL
authors.lastname: Myles
authors.affiliation: Department of Biological Sciences, Tennessee State University, Nashville, TN, USA. Electronic address: vtirivee@tnstate.edu.
authors.forename: Venkataswarup
authors.initials: V
authors.lastname: Tiriveedhi
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000276:immunology* / Q000503:physiopathology; D002273:Carcinogens / Q000494:pharmacology; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation; D020381:Interleukin-17 / Q000378:metabolism*; D012965:Sodium Chloride / Q000494:pharmacology*; D013312:Stress, Physiological / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002273:Carcinogens; D053503:Epithelial Sodium Channels; D020381:Interleukin-17; D012965:Sodium Chloride
keywords: Cancer; Cytokine; Epithelial sodium channel (ENaC); Inflammation; Interleukin-17