Effect of 1,24R-dihydroxyvitamin D3 on the growth of human keratinocytes.

Hdl Handle:
http://hdl.handle.net/10147/126103
Title:
Effect of 1,24R-dihydroxyvitamin D3 on the growth of human keratinocytes.
Authors:
Matsumoto, K; Hashimoto, K; Kiyoki, M; Yamamoto, M; Yoshikawa, K
Affiliation:
Department of Dermatology, Osaka University School of Medicine, Japan.
Citation:
Effect of 1,24R-dihydroxyvitamin D3 on the growth of human keratinocytes. 1990, 17 (2):97-103 J. Dermatol.
Journal:
The Journal of dermatology
Issue Date:
Feb-1990
URI:
http://hdl.handle.net/10147/126103
PubMed ID:
2158504
Abstract:
The effect of 1,24R-dihydroxyvitamin D3 (1,24R(OH)2D3), a synthetic analogue of a biologically active form of vitamin D3 (1,25-dihydroxyvitamin D3, 1,25(OH)2D3), on the growth of human keratinocytes cultured in serum-free medium was investigated. The growth of cultured normal human keratinocytes was inhibited by 65% by 10(-8)M 1,24R(OH)2D3 and by 90% by 10(-7)M 1,24(OH)2D3. It inhibited cell growth almost completely at 10(-6)M. The DNA synthesis of keratinocytes was also inhibited with 1,24R(OH)2D3 by 27% at 10(-8)M, 59% at 10(-7)M, and 92% at 10(-6)M. The inhibition of cell growth and DNA synthesis were more remarkable by 1,24R(OH)2D3 than by 1,25(OH)2D3. 1,24R(OH)2D3 also inhibited the growth of keratinocytes derived from patients with psoriasis vulgaris; the growth inhibitory effect was again more remarkable with 1,24R(OH)2D3 than with 1,25(OH)2D3. The viability and protein synthesis of keratinocytes were not affected by 1,24R(OH)2D3, suggesting that the growth inhibitory effect is due to its biological activity, not to cytotoxicity. The binding of [3H]-labeled 1,25(OH)2D3 to its receptor in the cytosolic fraction of cultured keratinocytes was competitively substituted by unlabeled 1,24R(OH)2D3 as well as 1,25(OH)2D3, suggesting that 1,24R(OH)2D3 binds to the 1,25(OH)2D3 receptor. It was found that the affinity of 1,24R(OH)2D3 for the receptor was slightly higher than that of 1,25(OH)2D3. These results demonstrate that 1,24R(OH)2D3 functions as a potent growth inhibitor in vitro in human keratinocytes from both normal and psoriatic epidermis, and it possesses a higher affinity for the 1,25(OH)2D3 receptor in cultured human keratinocytes. The difference in affinity of 1,24R(OH)2D3 for the 1,25(OH)2D3 receptor correlates with its greater inhibition of keratinocyte growth than 1,25(OH)2D3. 1,24R(OH)2D3 may be useful in the treatment of psoriasis.
Item Type:
Article
Language:
en
MeSH:
Binding, Competitive; Calcitriol; Cell Division; Cell Survival; Cells, Cultured; DNA; Dihydroxycholecalciferols; Humans; Keratinocytes; Protein Biosynthesis; Psoriasis; Receptors, Calcitriol; Receptors, Steroid
ISSN:
0385-2407

Full metadata record

DC FieldValue Language
dc.contributor.authorMatsumoto, Ken
dc.contributor.authorHashimoto, Ken
dc.contributor.authorKiyoki, Men
dc.contributor.authorYamamoto, Men
dc.contributor.authorYoshikawa, Ken
dc.date.accessioned2011-03-29T14:18:36Z-
dc.date.available2011-03-29T14:18:36Z-
dc.date.issued1990-02-
dc.identifier.citationEffect of 1,24R-dihydroxyvitamin D3 on the growth of human keratinocytes. 1990, 17 (2):97-103 J. Dermatol.en
dc.identifier.issn0385-2407-
dc.identifier.pmid2158504-
dc.identifier.urihttp://hdl.handle.net/10147/126103-
dc.description.abstractThe effect of 1,24R-dihydroxyvitamin D3 (1,24R(OH)2D3), a synthetic analogue of a biologically active form of vitamin D3 (1,25-dihydroxyvitamin D3, 1,25(OH)2D3), on the growth of human keratinocytes cultured in serum-free medium was investigated. The growth of cultured normal human keratinocytes was inhibited by 65% by 10(-8)M 1,24R(OH)2D3 and by 90% by 10(-7)M 1,24(OH)2D3. It inhibited cell growth almost completely at 10(-6)M. The DNA synthesis of keratinocytes was also inhibited with 1,24R(OH)2D3 by 27% at 10(-8)M, 59% at 10(-7)M, and 92% at 10(-6)M. The inhibition of cell growth and DNA synthesis were more remarkable by 1,24R(OH)2D3 than by 1,25(OH)2D3. 1,24R(OH)2D3 also inhibited the growth of keratinocytes derived from patients with psoriasis vulgaris; the growth inhibitory effect was again more remarkable with 1,24R(OH)2D3 than with 1,25(OH)2D3. The viability and protein synthesis of keratinocytes were not affected by 1,24R(OH)2D3, suggesting that the growth inhibitory effect is due to its biological activity, not to cytotoxicity. The binding of [3H]-labeled 1,25(OH)2D3 to its receptor in the cytosolic fraction of cultured keratinocytes was competitively substituted by unlabeled 1,24R(OH)2D3 as well as 1,25(OH)2D3, suggesting that 1,24R(OH)2D3 binds to the 1,25(OH)2D3 receptor. It was found that the affinity of 1,24R(OH)2D3 for the receptor was slightly higher than that of 1,25(OH)2D3. These results demonstrate that 1,24R(OH)2D3 functions as a potent growth inhibitor in vitro in human keratinocytes from both normal and psoriatic epidermis, and it possesses a higher affinity for the 1,25(OH)2D3 receptor in cultured human keratinocytes. The difference in affinity of 1,24R(OH)2D3 for the 1,25(OH)2D3 receptor correlates with its greater inhibition of keratinocyte growth than 1,25(OH)2D3. 1,24R(OH)2D3 may be useful in the treatment of psoriasis.-
dc.language.isoenen
dc.subject.meshBinding, Competitive-
dc.subject.meshCalcitriol-
dc.subject.meshCell Division-
dc.subject.meshCell Survival-
dc.subject.meshCells, Cultured-
dc.subject.meshDNA-
dc.subject.meshDihydroxycholecalciferols-
dc.subject.meshHumans-
dc.subject.meshKeratinocytes-
dc.subject.meshProtein Biosynthesis-
dc.subject.meshPsoriasis-
dc.subject.meshReceptors, Calcitriol-
dc.subject.meshReceptors, Steroid-
dc.titleEffect of 1,24R-dihydroxyvitamin D3 on the growth of human keratinocytes.en
dc.typeArticleen
dc.contributor.departmentDepartment of Dermatology, Osaka University School of Medicine, Japan.en
dc.identifier.journalThe Journal of dermatologyen
dc.description.provinceLeinster-

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