Abstract 180: Interleukin (IL) 16 Acts as a Regulator of Skin Electrolyte Metabolism and Blood Pressure
We showed that Na+ is stored in the skin without commensurate water retention. In response to interstitial electrolyte load, mononuclear phagocyte system (MPS) cells secrete VEGF C, as regulated by tonicity enhancer binding protein (TonEBP) attaching to the VEGF C promoter. VEGF C induces hyperplasia of skin lymphcapillaries. As IL16 harbors a TonEBP binding site, we tested the hypothesis that IL16 participates in this process. We cultured bone marrow-derived macrophages in isotonic or hypertonic cell culture media and measured IL16 expression. We fed male FVB mice a low salt diet (LSD; < 0.1% NaCl + tap) or a high salt diet (HSD; 4% NaCl + 0.9% saline) for two weeks. We treated the groups with either IL16 specific antibodies or no antibody. After two weeks we measured mean arterial blood pressure (MAP), skin Na+, Cl-, and water content (rSKNa, rSKCl, rSKW), quantified lymphcapillary density, VEGF C and TonEBP expression. IL16 was specifically secreted from macrophages in response to hypertonicity in vitro. HSD increased skin electrolytes, activated TonEBP/VEGF C, and resulted in lymphcapillary hyperplasia. Anti IL16 treatment under LSD increased skin electrolyte, water content and MAP. The IL16 antibody blunted the VEGF C driven lymphcapillary response despite salt load. No differences in skin electrolytes and MAP were found between IL16 antibody treated and untreated mice after HSD. We conclude that IL16 is a regulator of electrolyte and water metabolism and MAP, even in the absence of HSD. The finding that the IL16 promoter contains a TonEBP binding site suggests that IL16 could act as an osmoprotective gene that is involved in regulation of electrolyte homeostasis and MAP control.
- © 2012 by American Heart Association, Inc.