title: Tirilazad amelioriates extracellular effects of photooxidative stress by sealing the membrane of UVA irradiated human dermal fibroblasts.
abstract: The evaluation of antioxidant medication might provide further tools to protect the skin against the detrimental effects of photooxidative stress. In this context we have previously shown that the lazaroid tirilazad protects fibroblasts effectively against lipid peroxidation (LPO). Now we investigated whether and how tirilazad also influences two typical stress responses after UVA exposure, i.e. IL-6 and collagenase (MMP-1) release. Fibroblasts pre-incubated with tirilazad at a concentration of 30 microM show significantly less IL-6 in the extracellular medium after UVA exposure. Correspondingly, pre-incubation with tirilazad also significantly diminishes the extracellular MMP-1 protein concentration 24h post-irradiation. These effects observed are due to a membrane stabilisation, as tirilazad neither diminishes IL-6 mRNA production nor intracellular IL-6/MMP-1 protein levels after UVA exposure and thus most likely acts by sealing off the cell, delaying the typical leakage of IL-6 and MMP-1.
authors.affiliation: Department of Dermatology and Allergology, University of Ulm, Maienweg 12, D-89081 Ulm, Germany.
authors.forename: Lars Alexander
authors.initials: LA
authors.lastname: Schneider
authors.forename: Joachim
authors.initials: J
authors.lastname: Dissemond
authors.forename: Edith
authors.initials: E
authors.lastname: Schwamborn
authors.forename: Meinhard
authors.initials: M
authors.lastname: Wlaschek
authors.forename: Peter
authors.initials: P
authors.lastname: Brenneisen
authors.forename: Karin
authors.initials: K
authors.lastname: Scharffetter-Kochanek
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects*; D011281:Pregnatrienes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D014466:Ultraviolet Rays
chemical_list: D000975:Antioxidants; D015850:Interleukin-6; D011281:Pregnatrienes; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D020781:Matrix Metalloproteinase 1; C053355:tirilazad