Ultraviolet B radiation regulates cysteine-rich protein 1 in human keratinocytes.
BACKGROUND
Cysteine-rich protein 1 (CRP1) is a growth-inhibitory cytoskeletal protein that is induced by ultraviolet (UV) C radiation radiation in fibroblasts. Our aim was to investigate the effects of UV radiation on CRP1 in keratinocytes, the main cell type subjected to UV radiation in the human body.


METHODS
The effects of physiologically relevant doses of UVB radiation on CRP1 protein levels were studied in cultured primary keratinocytes and transformed cell lines (HaCaT, A-431) by immunoblotting. UVB-induced keratinocyte apoptosis was assessed by flow cytometry and monitoring caspase activity. Expression of CRP1 in human skin in vivo was studied by immunohistochemistry in samples of normal skin, actinic keratosis (AK) representing UV-damaged skin and squamous cell carcinoma (SCC), a UV-induced skin cancer.


RESULTS
CRP1 expression increased by UVB radiation in primary but not in immortalized keratinocytes. Upon high, apoptosis-inducing doses of UV radiation, CRP1 was cleaved in a caspase-dependent manner. In normal skin, CRP1 was expressed in smooth muscle cells, vasculature, sweat glands, sebaceous glands and hair root sheath, but very little CRP1 was present in keratinocytes. CRP1 expression was elevated in basal cells in AK but not in SCC.


CONCLUSIONS
CRP1 expression is regulated by UVB in human keratinocytes, suggesting a role for CRP1 in the phototoxic responses of human skin.
Latonen
Leena
L
Haartman Institute, University of Helsinki, Helsinki, Finland. leena.latonen@helsinki.fi
Järvinen
Päivi M
PM
Suomela
Sari
S
Moore
Henna M
HM
Saarialho-Kere
Ulpu
U
Laiho
Marikki
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000528:radiation effects*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D055623:Keratosis, Actinic / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis*; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology; D014466:Ultraviolet Rays / Q000009:adverse effects*
D009687:Nuclear Proteins; D020169:Caspases