title: Heme oxygenase-1 induction attenuates corneal inflammation and accelerates wound healing after epithelial injury.
abstract: OBJECTIVE
  Heme oxygenase (HO) is considered a fundamental endogenous immunomodulatory, cytoprotective, and anti-inflammatory system. This protective function is primarily ascribed to the inducible HO-1. The authors examined the effect of HO-1 induction on corneal inflammation and wound healing in mice undergoing epithelial injury.
  
  
  METHODS
  C57BL6 mice were treated with SnCl(2) the day before epithelial injury and once daily thereafter. The corneal epithelium was removed with the use of a corneal rust ring remover in anesthetized mice. Reepithelialization was measured by fluorescein staining. The inflammatory response was examined by histology and was quantified by the myeloperoxidase assay. Inflammatory lipid mediators were detected and quantified by LC/MS/MS-based lipidomic analysis. HO-1 expression was assessed by real-time PCR, and HO activity was determined by measuring HO-dependent carbon monoxide production.
  
  
  RESULTS
  Epithelial injury caused a time-dependent transient increase in HO-1 expression and HO activity that was significantly amplified by treatment with SnCl(2), resulting in a twofold to threefold increase in mRNA levels and a similar increase in corneal HO activity. Induction of HO-1 was associated with a significant acceleration of wound healing when compared with a vehicle-treated group and with attenuation of the inflammatory response, evidenced by a significant decrease in the number of infiltrating cells and by a significant reduction in the expression and production of proinflammatory lipid mediators and cytokines.
  
  
  CONCLUSIONS
  Increased expression of HO-1 provides a mechanism that modulates inflammation and promotes wound closure; pharmacologic amplification of this system may constitute a novel strategy to treat corneal inflammation while accelerating wound repair after injury.
authors.affiliation: Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA.
authors.forename: Kiran
authors.initials: K
authors.lastname: Patil
authors.forename: Lars
authors.initials: L
authors.lastname: Bellner
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cullaro
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Gotlinger
authors.forename: Michael W
authors.initials: MW
authors.lastname: Dunn
authors.forename: Michal Laniado
authors.initials: ML
authors.lastname: Schwartzman
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D054426:Chemokine CXCL2 / Q000378:metabolism; D002853:Chromatography, Liquid; D004790:Enzyme Induction / Q000187:drug effects; D019573:Epithelium, Corneal / Q000293:injuries / Q000502:physiology*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D053582:Interleukin-1alpha / Q000378:metabolism; D007634:Keratitis / Q000201:enzymology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D017971:Tin Compounds / Q000494:pharmacology; D014945:Wound Healing / Q000502:physiology*
chemical_list: D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D053582:Interleukin-1alpha; D012333:RNA, Messenger; D017971:Tin Compounds; C023599:stannous chloride; D009195:Peroxidase; D001189:Aryl Hydrocarbon Hydroxylases; C095029:cytochrome P-450 CYP4B1; D051547:Heme Oxygenase-1