The long-term goal of this research is to determine the molecular mechanism(s) whereby ultraviolet radiation (UVR)-induced cell injury regulates the human ornithine decarboxylase gene in skin and how agents such as retinoic acid modulate the cellular response to UVR-induced cell injury. This project will lead to a mechanistic understanding of how ultraviolet radiation and retinoid combined therapy improves psoriasis and allow us to test better retinoids and phototherapies to better treat psoriasis.
SPECIFIC AIMS : (1) To define the effect of ultraviolet B (UVB) on the ornithine decarboxylase enzyme activity in cultured human keratinocytes. (2) To determine whether the levels of ODC mRNA are increased in parallel with the UVB-induced increase in ODC enzyme activity. (3) To determine whether the increased level of ODC mRNA is the result of increased stability of the mRNA or whether it represents increased transcription of the ODC gene. (4) To examine the promoter of the human ODC gene to define which regions are necessary for UVB-induction of ODC gene transcription. (5) To evaluate the effect of retinoic acid on UVB induction of the ODC gene.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AR001838-05
Application #
2077307
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Project Start
1991-04-01
Project End
1996-03-31
Budget Start
1995-04-01
Budget End
1996-03-31
Support Year
5
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Dermatology
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Prystowsky, J H; Muzio, P J; Sevran, S et al. (1996) Effect of UVB phototherapy and oral calcitriol (1,25-dihydroxyvitamin D3) on vitamin D photosynthesis in patients with psoriasis. J Am Acad Dermatol 35:690-5
Prystowsky, J H; Knobler, E H; Muzio, P J (1996) Oral calcitriol (1,25-dihydroxyvitamin D3) does not augment UVB phototherapy for plaque psoriasis. J Am Acad Dermatol 35:272-4
Xue, G Z; Zheng, Z S; Chen, R Z et al. (1996) Phorbol 12-myristate 13-acetate inhibits epidermal growth factor signalling in human keratinocytes, leading to decreased ornithine decarboxylase activity. Biochem J 319 ( Pt 2):641-8
Zheng, Z S; Xue, G Z; Prystowsky, J H (1995) Regulation of the induction of ornithine decarboxylase in keratinocytes by retinoids. Biochem J 309 ( Pt 1):159-65
Zheng, Z S; Xue, G Z; Grunberger, D et al. (1995) Caffeic acid phenethyl ester inhibits proliferation of human keratinocytes and interferes with the EGF regulation of ornithine decarboxylase. Oncol Res 7:445-52
Zheng, Z S; Chen, R Z; Prystowsky, J H (1993) UVB radiation induces phosphorylation of the epidermal growth factor receptor, decreases EGF binding and blocks EGF induction of ornithine decarboxylase gene expression in SV40-transformed human keratinocytes. Exp Dermatol 2:257-65
Prystowsky, J H; Clevenger, C V; Zheng, Z S (1993) Inhibition of ornithine decarboxylase activity and cell proliferation by ultraviolet B radiation in EGF-stimulated cultured human epidermal keratinocytes. J Invest Dermatol 101:54-8
Prystowsky, J H; Clevenger, C V; Zheng, Z S (1993) Epidermal growth factor induces ornithine decarboxylase in SV40-immortalized human keratinocytes. Exp Dermatol 2:125-32