Identification of histamine receptors and reduction of squalene levels by an antihistamine in sebocytes.
Overproduction of sebum, especially during adolescence, is causally related to acne and inflammation. As a way to reduce sebum and its interference with the process of follicular keratinization in the pilosebaceous unit leading to inflammatory acne lesions, antihistamines were investigated for their effect on sebocytes, the major cell of the sebaceous gland responsible for producing sebum. Reverse transcriptase-PCR analysis and immunofluorescence of an immortalized sebocyte cell line (SZ95) revealed the presence of histamine-1 receptor (H-1 receptor), and thus indicated that histamines and, conversely, antihistamines could potentially modulate sebocyte function directly. When sebocytes were incubated with an H-1 receptor antagonist, diphenhydramine (DPH), at non-cytotoxic doses, a significant decrease in squalene levels, a biomarker for sebum, was observed. As determined by high-performance liquid chromatography, untreated sebocytes contained 6.27 (+/-0.73) nmol squalene per 10(6) cells, whereas for DPH-treated cells, the levels were 2.37 (+/-0.24) and 2.03 (+/-0.97) nmol squalene per 10(6) cells at 50 and 100 microM, respectively. These data were further substantiated by the identification of histamine receptors in human sebaceous glands. In conclusion, our data show the presence of histamine receptors on sebocytes, demonstrate how an antagonist to these receptors modulated cellular function, and may indicate a new paradigm for acne therapy involving an H-1 receptor-mediated pathway.
Pelle
Edward
E
Estee Lauder Research Laboratories, Melville, New York 11747, USA. epelle@estee.com
McCarthy
James
J
Seltmann
Holger
H
Huang
Xi
X
Mammone
Thomas
T
Zouboulis
Christos C
CC
Maes
Daniel
D
D000152:Acne Vulgaris / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004155:Diphenhydramine / Q000494:pharmacology*; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D011969:Receptors, Histamine H1 / Q000235:genetics* / Q000378:metabolism; D012627:Sebaceous Glands / Q000166:cytology / Q000502:physiology*; D012629:Sebum / Q000378:metabolism; D013185:Squalene / Q000378:metabolism*
D006634:Histamine H1 Antagonists; D011969:Receptors, Histamine H1; D013185:Squalene; D004155:Diphenhydramine