title: Degradation of superparamagnetic iron oxide nanoparticle-induced ferritin by lysosomal cathepsins and related immune response.
abstract: OBJECTIVE
  To examine the physiological impact of superparamagnetic iron oxide nanoparticles (SPIONs) on cell function and its interaction with oxysterol laden cells.
  
  
  METHODS
  Intracellular iron was determined by Prussian blue staining. Cellular ferritin, cathepsin L and ferroportin were analyzed by flow cytometry and fluorescence microscopy. Cytokine secretion was determined by ELISA and immunoblotting.
  
  
  RESULTS
  In U937 and THP 1 cells, we did not detect any loss of cell viability on SPION loading. Desferrioxamine prevents induction of both ferritin and cathepsin L by SPIONs. Inhibition of lysosomal cathepsins upregulates both endogenous- and SPION-induced ferritin. SPION loading induces membranous ferroportin and incites secretion of ferritin, TNF-α and IL-10. 7β-hydroxycholesterol exposure reduces SPION uptake by cells.
  
  
  CONCLUSIONS
  SPION loading results in upregulation of lysosomal cathepsin, membranous ferroportin and ferritin degradation, which is associated with secretion of both pro- and anti-inflammatory cytokines. A reduced SPION uptake by oxysterol-laden cells may lead to a compromised MRI with elevated cathepsins and ferritin.
authors.affiliation: Division of Experimental Pathology, Department of Clinical & Experimental Medicine, Faculty of Health Sciences, Linkoping University, Linköping 58185, Sweden.
authors.forename: Amit
authors.initials: A
authors.lastname: Laskar
authors.forename: Moumita
authors.initials: M
authors.lastname: Ghosh
authors.forename: Sikander Iqbal
authors.initials: SI
authors.lastname: Khattak
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Xi-Ming
authors.initials: XM
authors.lastname: Yuan
mesh_terms: D002403:Cathepsins / Q000378:metabolism; D027682:Cation Transport Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D005290:Ferric Compounds / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D005293:Ferritins / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007110:Immunity, Active / Q000187:drug effects; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D058185:Magnetite Nanoparticles / Q000009:adverse effects / Q000737:chemistry; D008856:Microscopy, Fluorescence; D059748:Proteolysis; D000098742:Ferroportin
chemical_list: D027682:Cation Transport Proteins; D003287:Contrast Media; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D000098742:Ferroportin; C000499:ferric oxide; D005293:Ferritins; D002403:Cathepsins