Astaxanthin attenuates the UVB-induced secretion of prostaglandin E2 and interleukin-8 in human keratinocytes by interrupting MSK1 phosphorylation in a ROS depletion-independent manner.
To elucidate the effects of redox balance regulation on cutaneous inflammation, we used the potent antioxidant astaxanthin (AX) to assess its effect on the UVB-induced secretion of PGE(2) and IL-8 in human keratinocytes and analysed its biological mechanism of action. The addition of AX (at 8 [micro]m) to human keratinocytes even after UVB irradiation significantly down-regulated the increased secretion of PGE(2) or IL-8. Those suppressive effects were accompanied by significantly decreased expression of genes encoding COX-2 or IL-8 as well as COX-2 protein. Analysis using a specific NF-[kappa]B tanslocation inhibitor demonstrated that the UVB-stimulated secretion of PGE(2) and IL-8 was significantly abolished by its treatment prior to UVB irradiation. Western blotting of phosphorylated signalling molecules revealed that UVB irradiation (80 mJ/cm(2)) significantly stimulated the phosphorylation of p38, ERK and JNK, which was not suppressed by treatment with AX after irradiation. In contrast, AX significantly inhibited the UVB-increased phosphorylation of mitogen- and stress-activated protein kinase (MSK)-1, NF-[kappa]Bp65 or CREB even when treated postirradiation. Further, the MSK1 inhibitor H89 significantly down-regulated the increased secretion of PGE(2) and IL-8 in UVB-exposed human keratinocytes, following post-irradiation treatment. These findings suggests that AX attenuates the auto-phosphorylation of MSK1 required for its activation, which results in the decreased phosphorylation of NF-[kappa]Bp65, which in turn probably leads to a deficiency of NF-[kappa]B DNA binding activity. This may be associated with the significant suppression of PGE(2) /IL-8 secretion via the down-regulated expression of COX-2 and IL-8 at the gene and/or protein levels.
Exp Dermatol. 2012 Jul;21 Suppl 1:11-7
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|Article Type:||Brief article|
|Date:||Apr 1, 2013|
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