title: UVB light regulates expression of antioxidants and inflammatory mediators in human corneal epithelial cells.
abstract: The cornea is highly sensitive to ultraviolet B (UVB) light-induced oxidative stress, a process that results in the production of inflammatory mediators which have been implicated in tissue injury. In the present studies, we characterized the inflammatory response of human corneal epithelial cells to UVB (2.5-25mJ/cm(2)). UVB caused a dose-dependent increase in the generation of reactive oxygen species in the cells. This was associated with increases in mRNA expression of the antioxidants Cu,Zn superoxide dismutase (SOD), Mn-SOD, catalase and heme oxygenase-1 (HO-1), as well as the glutathione S-transferases (GST), GSTA1-2, GSTA3, GSTA4, GSTM1, and mGST2. UVB also upregulated expression of the proinflammatory cytokines, IFNγ, IL-1β, TGFβ and TNFα, and enzymes important in prostaglandin (PG) biosynthesis including cyclooxygenase-2 (COX-2) and the PG synthases mPGES-2, PGDS, PGFS and thromboxane synthase, and in leukotriene biosynthesis including 5-lipoxygenase (5-LOX), 15-LOX-2, and the epidermal and platelet forms of 12-LOX. UVB was found to activate JNK and p38 MAP kinases in corneal epithelial cells; ERK1/2 MAP kinase was found to be constitutively active, and its activity increased following UVB treatment. Inhibition of p38 blocked UVB-induced expression of TNFα, COX-2, PGDS and 15-LOX-2, while JNK inhibition suppressed TNFα and HO-1. These data indicate that UVB modulates corneal epithelial cell expression of antioxidants and proinflammatory mediators by distinct mechanisms. Alterations in expression of these mediators are likely to be important in regulating inflammation and protecting the cornea from UVB-induced oxidative stress.
authors.affiliation: Pharmacology and Toxicology, Rutgers University, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA. atblack@rci.rutgers.edu
authors.forename: Adrienne T
authors.initials: AT
authors.lastname: Black
authors.forename: Marion K
authors.initials: MK
authors.lastname: Gordon
authors.forename: Diane E
authors.initials: DE
authors.lastname: Heck
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gallo
authors.forename: Debra L
authors.initials: DL
authors.lastname: Laskin
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Laskin
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D001483:Base Sequence; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers; D019573:Epithelium, Corneal / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D000975:Antioxidants; D016207:Cytokines; D017931:DNA Primers; D018836:Inflammation Mediators; D012333:RNA, Messenger; D017382:Reactive Oxygen Species