β-carotene inhibits UVA-induced matrix metalloprotease 1 and 10 expression in keratinocytes by a singlet oxygen-dependent mechanism

UVA exposure causes skin photoaging by singlet oxygen 1O2-mediated induction of, e.g., matrix metalloproteases (MMPs). We assessed whether pretreatment with β-carotene, a 1O2 quencher and retinoic acid (RA) precursor, interferes with UVA-induced gene regulation. HaCaT keratinocytes were precultured with β-carotene at physiological concentrations (0.5, 1.5, and 3.0 μM) prior to exposure to UVA from a Honle solar simulator (270 kJ/m2). HaCaT cells accumulated β-carotene in a time- and dose-dependent manner. UVA irradiation massively reduced the cellular β-carotene content. β-Carotene suppressed UVA-induction of MMP-1, MMP-3, and MMP-10, three major matrix metalloproteases involved in photoaging. We show that regulation by not only MMP-1, but also MMP-10, involves 1O2-dependent mechanisms. β-Carotene dose-dependently quenched 1O2-mediated induction of MMP-1 and MMP-10. Thus, as in chemical solvent systems, β-carotene quenches 1O2 also in living cells. Vitamin E did not cooperate with β-carotene to further inhibit MMP induction. HaCaT cells produced weak retinoid activity from β-carotene, as demonstrated by mild upregulation of RARβ and activation of an RARE-dependent reporter gene. β-Carotene did not regulate the genes encoding other RARs, RXRs, or the two β-carotene cleavage enzymes. These results demonstrate that β-carotene acts photoprotectively, and that this effect is mediated by 1O2 quenching.