Modelling the remission of individual acne lesions in vitro.
BACKGROUND
Acne lesions spontaneously remit, but the mechanism of this remission has not been elaborated. It is known, however, that the remission is associated with a de-differentiation of sebocytes, causing a cessation of sebum secretion specific to that particular pilosebaceous unit. We have previously described the cytokines that will promote in vitro the lesions of acne.


OBJECTIVE
To show that those same cytokines may also promote a de-differentiation of sebocytes analogous to that seen during remission of some lesions.


METHODS
Human chest sebaceous glands were maintained in vitro as whole organs. We then chronicled the effects of the appropriate cytokines and growth factors on the glandular rates of (i) lipogenesis and (ii) DNA synthesis, as well as on (iii) glandular morphology, (iv) the expression patterns of the proliferation marker Ki-67, (v) keratinocyte-specific markers, and (vi) the sebocyte marker epithelial membrane antigen.


RESULTS
We have shown that the same cytokines that promote comedogenesis (interleukin-1alpha), expression of infundibular intercellular adhesion molecule-1 and human leucocyte-associated antigen-DR (tumour necrosis factor-alpha and interferon-gamma), and infundibular disruption (epidermal growth factor/transforming growth factor-alpha) in human infundibula in vitro, will also inhibit sebaceous lipogenesis in vitro and will also induce, histologically, a de-differentiation of human sebocytes into a keratinocyte-like phenotype.


CONCLUSIONS
These results confirm our hypothesis that the cytokines that induce the infundibular changes in acne may also inhibit the secretion of lipid from the sebaceous gland and thus, on diffusing down to the gland, contribute to the remission of the individual lesions. These findings help to explain the known natural history of the disease.
Downie
M M T
MM
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital Box 232, Hills Road, Cambridge CB2 2QR, U.K. mdownie@incyte.com
Sanders
D A
DA
Kealey
T
T
D000152:Acne Vulgaris / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D008055:Lipids / Q000096:biosynthesis; D008297:Male; D008954:Models, Biological; D009924:Organ Culture Techniques; D012075:Remission, Spontaneous; D012627:Sebaceous Glands / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D016207:Cytokines; D006133:Growth Substances; D008055:Lipids