Tirilazad amelioriates extracellular effects of photooxidative stress by sealing the membrane of UVA irradiated human dermal fibroblasts.
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.
Schneider
Lars Alexander
LA
Department of Dermatology and Allergology, University of Ulm, Maienweg 12, D-89081 Ulm, Germany.
Dissemond
Joachim
J
Schwamborn
Edith
E
Wlaschek
Meinhard
M
Brenneisen
Peter
P
Scharffetter-Kochanek
Karin
K
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
D000975:Antioxidants; D015850:Interleukin-6; D011281:Pregnatrienes; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D020781:Matrix Metalloproteinase 1; C053355:tirilazad