Volume 84, Number 1, 75-87, DOI: 10.1007/s00109-005-0715-8

Enzymes involved in the biosynthesis of leukotriene B4 and prostaglandin E2 are active in sebaceous glands

Theodosios Alestas, Ruta Ganceviciene, Sabine Fimmel, Karin Müller-Decker and Christos C. Zouboulis

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Abstract

The expression of enzymes involved in leukotriene and prostaglandin signalling pathways, of interleukins 6 and 8 and of peroxisome proliferator-activated receptors in sebaceous glands of acne-involved facial skin was compared with those of non-involved skin of acne patients and of healthy individuals. Moreover, 5-lipoxygenase and leukotriene A4 hydrolase were expressed at mRNA and protein levels in vivo and in SZ95 sebocytes in vitro (leukotriene A4 hydrolase > 5-lipoxygenase), while 15-lipoxygenase-1 was only detected in cultured sebocytes. Cyclooxygenase-1 and cyclooxygenase-2 were also present. Peroxisome proliferator-activated receptors were constitutively expressed. Enhanced 5-lipoxygenase, cyclooxygenase 2 and interleukin 6 expression was detected in acne-involved facial skin. Arachidonic acid stimulated leukotriene B4 and interleukin 6 release as well as prostaglandin E2 biosynthesis in SZ95 sebocytes, induced abundant increase in neutral lipids and down-regulated peroxisome proliferator-activated receptor-agr, but not receptor-gamma1 mRNA levels, which were the predominant peroxisome proliferator-activated receptor isotypes in SZ95 sebocytes. In conclusion, human sebocytes possess the enzyme machinery for functional leukotriene and prostaglandin pathways. A comprehensive link between inflammation and sebaceous lipid synthesis is provided.

Keywords  Arachidonic acid - Lipoxygenase - Cyclooxygenase - Sebaceous glands - Acne

T. Alestas and R. Ganceviciene contributed equally to the study

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