Effect of insulin-like growth factor-I/somatomedin C on thymidine incorporation in cultured psoriatic keratinocytes after growth arrest in growth factor-free medium.
Near confluent cultures of human keratinocytes will arrest in GO/G1 of the cell cycle when they are placed into growth factor (GF)-free medium with a Ca++ concentration below 0.1 mM for 4 days. Addition of certain growth factors will stimulate the cell to re-enter the growth cycle and move into the S-phase after 7-12 h. Insulin-like growth factor/somatomedin C (IGF-I) was found to be the most active factor in promoting 3H-dT incorporation among several growth factors evaluated in this system. This system was applied to keratinocytes cultured from uninvolved skin of psoriatic patients and keratinocytes from clinically healthy skin of nonpsoriatic control persons. 3H-dT incorporation in response to 50 ng IGF-I per ml medium was significantly more stimulated in psoriatic keratinocytes (7.0 +/- 0.41 fold) than in normal keratinocytes (2.9 +/- 0.49 fold). There was no significant difference between the age of donors or the time cells were in culture when the measurements were performed. The stimulatory effect became even more apparent when cultures were growth-arrested in the presence of heparin, which mainly causes a suppression of the 'background' incorporation of 3H-dT occurring in the absence of exogenous GF (psoriatic: 35.0 +/- 2.2 fold; normal: 9.3 +/- 2.1 fold). The increased response of psoriatic keratinocytes to IGF-I does not appear to be related to a difference in time required for the cells to traverse from the presumed restriction point in GO/G1 to the beginning of S (7-10 h) and the middle of S (approximately 19 h).(ABSTRACT TRUNCATED AT 250 WORDS)
Ristow
H J
HJ
Dermatology Service, Veterans Affairs Medical Center, Decatur, GA 30033.
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D003470:Culture Media; D004247:DNA / Q000096:biosynthesis; D006133:Growth Substances / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D011565:Psoriasis / Q000378:metabolism*; D012016:Reference Values; D013936:Thymidine / Q000378:metabolism*
D003470:Culture Media; D006133:Growth Substances; D007334:Insulin-Like Growth Factor I; D006493:Heparin; D004247:DNA; D013936:Thymidine