ZIP14 regulates tight junction protein expression in response to LPS

Abstract

ZIP14 is a member of the SLC39A family of zinc transporters, which uptake zinc into the cytoplasmic compartment of cells. This transporter exhibits differential tissue distribution with the intestines comprising a large relative expression level. In response to low dose lipopolysaccharide (LPS), ZIP14 expression and localization to the plasma membrane increases. In an intestinal cell model, zinc administered directly to the cells can alter the expression of tight junction (TJ) proteins. The purpose of this study is to determine if the increased ZIP14 expression during acute inflammation in the small intestines alters TJ protein expression. In vivo experiments were performed using wild type and ZIP14 ‐/‐ mice treated with intraperitoneal injections containing either saline or 2 mg/kg LPS. In vitro experiments utilized the rat intestinal cell line IEC‐6. Knockdown experiments were performed with ZIP14 siRNA on IEC‐6 cells treated with conditioned media from differentiated THP‐1 cells activated with H2O or 100 ng/mL LPS for 24 hrs. Overexpression of a ZIP14 vector for 48 hrs in IEC‐6 cells was also performed. In response to LPS stimuli, TJ protein expression was altered both in vivo and in vitro. The response of TJ proteins to LPS stimulation was altered in experimental groups lacking adequate ZIP14 expression. ZIP14 may confer a protective effect to acute LPS challenge through TJ proteins.