title: Nona-D-arginine amide suppresses corneal cytokines in Pseudomonas aeruginosa keratitis.
abstract: OBJECTIVE
  Nona-D-arginine (D9R) amide suppressed interleukin 1β production during Pseudomonas aeruginosa corneal infection. The purpose of this study was to determine the cellular disposition of D9R and its effect on other inflammatory mediators induced by infection.
  
  
  METHODS
  Mouse eyes received 5 μL of either phosphate-buffered saline (PBS, pH 7.4) or 100-μM D9R hourly for 5 hours (total of 6 drops per eye) immediately after corneal wounding and infection with 1 × 10 colony-forming units (CFUs) of P. aeruginosa strain PAO1. At 6, 12, and 24 hours postinfection, eyes were scored on a scale of 0 (normal eye) to +4 (corneal perforation). After scoring, mice were killed and eyes enucleated. Whole eyes were used for determining viable CFUs per eye. Corneas were excised for quantitation of tumor necrosis factor α, interferon γ, interleukin 10, and granulocyte-macrophage colony-stimulating factor. The fate of D9R in cells was determined using a labeled peptide.
  
  
  RESULTS
  Eyes treated with D9R had significantly lower disease scores (P ≤ 0.001) and fewer CFUs (P ≤ 0.01) than those in PBS-treated eyes. No corneal cytokines were detected in any D9R-treated eyes. In contrast, beginning at 12 hours postinfection, increasing amounts of tumor necrosis factor alpha, interleukin 10, and granulocyte-macrophage colony-stimulating factor were detectible in corneas of PBS-treated eyes. Within 60 minutes, D9R accumulated in the cell nucleus and nucleolus and remained for over 24 hours.
  
  
  CONCLUSIONS
  D9R reduces the severity of P. aeruginosa ocular infection in part by reducing bacterial burden and in part by controlling a destructive proinflammatory response. D9R might be a useful alternative to steroids in treating other inflammation-mediated pathologies of the eye.
authors.affiliation: Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Karicherla
authors.forename: Siddhesh
authors.initials: S
authors.lastname: Aras
authors.forename: Ashok
authors.initials: A
authors.lastname: Aiyar
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Hobden
mesh_terms: D000818:Animals; D058491:Bacterial Load; D003315:Cornea / Q000378:metabolism*; D016207:Cytokines / Q000037:antagonists & inhibitors*; D005260:Female; D017930:Genes, Reporter; D007634:Keratitis / Q000382:microbiology* / Q000473:pathology; D008156:Luciferases / Q000235:genetics; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000493:pharmacokinetics / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000378:metabolism*; D011550:Pseudomonas aeruginosa; D012720:Severity of Illness Index; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D016207:Cytokines; D009842:Oligopeptides; C555621:nonaarginine amide; D008156:Luciferases
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