Analysis of the Mechanism of Ultraviolet (UV) B Radiation – Induced Prostaglandin E2 Synthesis by Human Epidermoid Carcinoma Cells

Grewe, Markus; Trefzer, Uwe; Ballhorn, Annette; Gyufko, Karin; Henninger, Hanspeter; Krutmann, Jean

doi:10.1111/1523-1747.ep12365904

Cited by 102 publications

(67 citation statements)

References 24 publications

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Section: Discussionmentioning

confidence: 99%

“…27) PGE 2 , the primary prostaglandin released after PAR-2 activation, is a potent stimulus for melanocyte dendrite formation. 19,25,27) In the present study, macelignan significantly reduced PGE 2 secretion by keratinocytes co-cultured with B16F10 melanoma cells. This finding is consistent with that of our previous study, which demonstrated that macelignan decreased COX-2 expression in UVB-irradiated HaCaT cells through mitogen-activated protein kinase (MAPK) signaling and the phosphoinositide 3-kinase (PI3K)/Akt pathway.…”

Section: Discussionmentioning

confidence: 99%

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Macelignan Inhibits Melanosome Transfer Mediated by Protease-Activated Receptor-2 in Keratinocytes

Choi

Kang

Kim

et al. 2011

Biological & Pharmaceutical Bulletin

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Skin pigmentation is the result of melanosome transfer from melanocytes to keratinocytes. Protease-activated receptor-2 (PAR-2) is a key mediator of melanosome transfer, which occurs as the melanocyte extends its dendrite toward surrounding keratinocytes that take up melanosomes by phagocytosis. We investigated the effects of macelignan isolated from Myristica fragrans HOUTT. (nutmeg) on melanosome transfer and the regulation of PAR-2 in human keratinocytes (HaCaT). HaCaT cells stimulated by the PAR-2-activating peptide Ser-Leu-IleGly-Arg-Leu-NH 2 (SLIGRL) were treated with macelignan; PAR-2 expression was then determined by reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and immunocytochemistry. We evaluated the effects of macelignan on calcium mobilization and keratinocyte phagocytosis. In addition, B16F10 melanoma cells and keratinocytes were co-cultured to assess the effects of macelignan on prostaglandin E 2 (PGE 2 ) secretion and subsequent dendrite formation. Macelignan decreased HaCaT PAR-2 mRNA and protein levels in a dose-dependent manner. Furthermore, macelignan markedly reduced intracellular calcium mobilization and significantly downregulated keratinocyte phagocytosis, as shown by decreased ingestion of Escherichia coli bioparticles and fluorescent microspheres. In co-culture experiments, macelignan reduced keratinocyte PGE 2 secretion, thereby preventing dendrite formation in B16F10 melanoma cells compared with SLIGRL-treated controls. Macelignan inhibits melanosome transfer by downregulating PAR-2, thereby reducing keratinocyte phagocytosis and PGE 2 secretion, which in turn inhibits dendrite formation in B16F10 melanoma cells. Taken together, our findings suggest that macelignan could be used as a natural depigmenting agent to ameliorate hyperpigmentation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Macelignan Inhibits Melanosome Transfer Mediated by Protease-Activated Receptor-2 in Keratinocytes

Choi

Kang

Kim

et al. 2011

Biological & Pharmaceutical Bulletin

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“…Work from this laboratory has demonstrated that UVBinduction of Akt, a downstream component of the PI 3-kinase signaling pathway, results in upregulation of COX-2 in HaCaT cells . Induction of Cox-2 causes increased prostaglandin synthesis, a phenomenon associated with UV-induced tumorigenesis (Fischer et al, 1999;Grewe et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

The role of PI 3-kinase in the UVB-induced expression of c-fos

Gonzales¹,

Bowden²

2002

Oncogene

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The role of the PI 3-kinase signaling pathway in UVBinduced c-fos gene expression was investigated in a human keratinocyte cell line, HaCaT. The enzymatic activity of PI 3-kinase was increased threefold by 250 J/ m 2 UVB. Inhibition of PI 3-kinase activity, via expression of a mutant p85 subunit or treatment with wortmannin, resulted in decreased levels of c-fos promoter activity and c-fos protein. Two members of the PI 3-kinase signaling pathway, Akt and GSK-3b, were also found to aect c-fos transactivation. Expression of dominant negative Akt or wild-type GSK-3b signi®cantly inhibited UVB-induced c-fos promoter activity. In addition, when GSK-3b activity was inhibited by lithium chloride, both c-fos promoter activity and protein levels increased. These results demonstrate that both Akt activation and GSK-3b inactivation are required in the UVB-induction of c-fos. Our results demonstrate for the ®rst time that UVB induction of cfos is in part mediated by the PI 3-kinase signaling pathway in the HaCaT cell line. By identifying the multiple signaling pathways that are induced by UVB and contribute to the induction of c-fos expression, more drug targets may be identi®ed to aid attempts to prevent and treat skin cancer.

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“…Exposure of the skin to UV light has been shown to induce prostaglandin production (Grewe et al, 1993;Buckman et al, 1998). There is evidence to indicate that UV induced prostaglandin synthesis may contribute to UV induced tumorigenesis (Fischer et al, 1999;Grewe et al, 1993). The initial step in the synthesis of prostaglandins from arachidonic acid is catalyzed by cyclooxygenase(s).…”

mentioning

confidence: 99%

Role of p38 MAP kinases and ERK in mediating ultraviolet-B induced cyclooxygenase-2 gene expression in human keratinocytes

et al. 2001

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The roles of p38 MAP kinases and ERK in UVB induced cox-2 gene expression were studied in a human keratinocyte cell line, HaCaT. UVB signi®cantly increased cox-2 gene expression at both protein and mRNA levels. As we reported previously, p38 and ERK were signi®cantly activated after UVB irradiation in HaCaT cells. In addition, treating the cells with p38 inhibitor SB202190 or MEK inhibitor PD98059 speci®-cally inhibited UVB induced p38 or ERK activation, respectively. In this study, we further examined the roles of p38 and ERK in UVB induced cox-2 gene expression in HaCaT cells. We found that SB202190 strongly inhibited UVB induced COX-2 protein expression at di erent time points and various UVB doses. Furthermore, SB202190 markedly inhibited UVB induced cox-2 mRNA. Our data indicated that ERK did not play a role in UVB induced cox-2 gene expression in human keratinocytes since suppression of ERK did not signi®cantly alter UVB induced increase of COX-2 protein and mRNA. These results suggested, for the ®rst time, that activation of p38 is required for UVB induced cox-2 gene expression in human keratinocytes. Since cox-2 expression plays an important role in UV carcinogenesis, p38 could be a potential molecular target for chemoprevention of skin cancer. Oncogene (2001) 20, 3921 ± 3926.

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Analysis of the Mechanism of Ultraviolet (UV) B Radiation – Induced Prostaglandin E2 Synthesis by Human Epidermoid Carcinoma Cells

Cited by 102 publications

References 24 publications

Macelignan Inhibits Melanosome Transfer Mediated by Protease-Activated Receptor-2 in Keratinocytes

Macelignan Inhibits Melanosome Transfer Mediated by Protease-Activated Receptor-2 in Keratinocytes

The role of PI 3-kinase in the UVB-induced expression of c-fos

Role of p38 MAP kinases and ERK in mediating ultraviolet-B induced cyclooxygenase-2 gene expression in human keratinocytes

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