Abstract
The influence of ultraviolet B (UVB) radiation on transglutaminase 1 (TGase 1), a major factor that regulates skin keratinization, has not been sufficiently characterized especially at the gene or protein level. Thus, we determined whether UVB affects the expression of TGase 1 in human keratinocytes and clarified the intracellular stress signaling mechanism(s) involved. Exposure of human keratinocytes to UVB significantly up-regulated the expression of TGase 1 at the gene and protein levels. Treatment with inhibitors of p38, MEK, JNK or NFκB significantly abolished the UVB-stimulated protein expression of TGase 1. Treatment with astaxanthin immediately after UVB irradiation did not attenuate the increased phosphorylation of Ser536/Ser468NFκBp65, c-Jun, ATK-2 and CK2, and did not abrogate the increased or diminished protein levels of c-Jun/c-Fos or I-κBα, respectively. However, the same treatment with astaxanthin significantly abolished the UVB-stimulated expression of TGase 1 protein, which was accompanied by the attenuated phosphorylation of Thr565/Ser376/Ser360MSK1, Ser276NFκBp65 and Ser133CREB. The MSK1 inhibitor H89 significantly down-regulated the increased protein expression of TGase 1 in UVB-exposed human keratinocytes, which was accompanied by an abrogating effect on the increased phosphorylation of Ser276NFκBp65 and Ser133CREB but not Thr565/Ser376/Ser360MSK1. Transfection of human keratinocytes with MSK1 siRNA suppressed the UVB-stimulated protein expression of TGase 1. These findings suggest that the UVB-stimulated expression of TGase 1 is mediated predominantly via the NFκB pathway and can be attenuated through a specific interruption of the p38/MSK1/NFκBp65Ser276 axis.
Highlights
Exposure of the skin to ultraviolet B (UVB) radiation causes inflammation and subsequent hyperkeratosis of the epidermis [1]
When stress-activated signaling inhibitors for p38, MEK and JNK or the NFκB translocation inhibitor JSH23 were added to Human primary keratinocytes (HPKs) 3 h before UVB irradiation and levels of transglutaminase 1 (TGase 1) were measured by western blotting at 48 h post-irradiation, increased levels of TGase 1 protein were significantly abrogated by all stress-activated signaling inhibitors tested (Fig 2)
When AX was added at a concentration of 1, 4 or 8 μM to HPKs 3 h before UVB exposure at 80 mJ/cm2, the increased level of TGase 1 at 48 h post-irradiation was significantly abrogated to the non-irradiated control level at the concentrations of 4 and 8 μM (Fig 3A)
Summary
Exposure of the skin to ultraviolet B (UVB) radiation causes inflammation and subsequent hyperkeratosis of the epidermis [1]. Hyperkeratotic skin is characterized by a roughened and toughened surface due to the formation of a hardened and thickened cornified cell envelope. The ceramide level in the stratum corneum is known to be markedly up-regulated within several days after UVB radiation [2]. Since the UVB-induced roughened skin could not be reasonably accounted for by the increased level of ceramides in the stratum corneum, little is known about the mechanism(s) involved in UVB-induced effects that result in the roughened and toughened skin. We hypothesized that the UVB-induced roughened skin might result from a thickened cornified cell envelope, which could be caused by an increase in the enzyme activity of transglutaminase(s) (TGases)
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