DIBI, a novel polymeric iron chelator modulates IL-6 and IL-8 secretion from Cystic Fibrosis airway epithelial cells in response to endotoxin induction
Affiliations: [a]
Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada
| [b] Chelation Partners Inc., Halifax, NS, Canada
| [c]
Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, NS, Canada
Correspondence:
[*]
Corresponding author: Christian Lehmann; Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada. E-mail: chlehmann@dal.ca.
Abstract: Iron chelators have been utilized clinically to treat patients with iron overload conditions. There is a growing body of evidence linking iron dysregulation and reactive oxygen species (ROS) overproduction as underlying factors in Cystic Fibrosis (CF) disease. The chronic inflammation can lead to progressive airway destruction. Alleviation of this chronic inflammation is a potential target for CF treatment and thus, this research investigated the dose-response effects of DIBI, a novel iron chelator, on inflammation in CF nasal epithelial cells. Polarized CF cells were stimulated with, lipopolysaccharide (LPS), co-treated with DIBI (LPS+DIBI), or DIBI alone (DIBI). We demonstrated that DIBI modulated the release of IL-6 and IL-8 in CF cells in a dose-dependent manner. Reduction of extracellular iron with the lower doses of DIBI (25 and 50μM), increased IL-6 secretion in non-induced cells. LPS challenge increased IL-6 and IL-8 secretion which was suppressed by high dose (200μM) DIBI administration. This study demonstrates the therapeutic potential of iron chelation therapy to treat the dysregulation of the immune response in CF patients.
Keywords: Inflammation, epithelial cells, Cystic Fibrosis, iron, iron chelation
