Modeling acne in vitro.
To help elucidate the factors responsible for the infundibular changes seen in acne, the human sebaceous pilosebaceous infundibulum was isolated by microdissection and maintained for 7 d in keratinocyte serum-free medium supplemented with 50 micrograms/ml bovine pituitary extract, 100 units/ml penicillin and streptomycin, 2.5 micrograms/ml amphotericin B and CaCl2(10H2O) to give a final Ca2+ concentration of 2 mM. Infundibular structure was maintained over 7 d in this medium; the pattern of cell division mimicked that in vivo. The rate of cell division was significantly higher than previously described for infundibula maintained in supplemented William's E medium, and moreover did not fall over 7 d. The addition of 1 ng/ml interleukin-1 alpha (IL-1 alpha) caused hypercornification of the infundibulum similar to that seen in comedones; this could be blocked by 1000 ng/ml interleukin-1 receptor antagonist (IL-1ra). In about 20% of subjects there was spontaneous hypercornification of the infundibulum that could be blocked by 1000 ng/ml IL-1ra, suggesting that the infundibulum is capable of synthesising IL-1 alpha. The addition of 5 ng/ml epidermal growth factor or 5 ng/ml transforming growth factor-alpha to the medium caused a disorganisation of the keratinocytes of the infundibulum that resulted in rupturing similar to that seen in the more severe, purulent grades of acne. The addition of 1 microM 13-cis retinoic acid caused a significant reduction in the rate of DNA synthesis and apparent parakeratosis. We are now, therefore, able to model histologically the major infundibular changes in acne.
Guy
R
R
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, U.K.
Green
M R
MR
Kealey
T
T
D000152:Acne Vulgaris / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D002417:Cattle; D002470:Cell Survival; D046508:Culture Techniques; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015474:Isotretinoin / Q000494:pharmacology; D007633:Keratins / Q000096:biosynthesis; D010241:Parakeratosis / Q000139:chemically induced; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D007375:Interleukin-1; D004815:Epidermal Growth Factor; D007633:Keratins; D015474:Isotretinoin