Enzymes involved in the biosynthesis of leukotriene B4 and prostaglandin E2 are active in sebaceous glands.
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 A(4) hydrolase were expressed at mRNA and protein levels in vivo and in SZ95 sebocytes in vitro (leukotriene A(4) 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 B(4) and interleukin 6 release as well as prostaglandin E(2) biosynthesis in SZ95 sebocytes, induced abundant increase in neutral lipids and down-regulated peroxisome proliferator-activated receptor-alpha, 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.
Alestas
Theodosios
T
Department of Dermatology, Charité Universitaetsmedizin Berlin, Campus Benjamin Franklin, Fabeckstrasse 60-62, 14195 Berlin, Germany.
Ganceviciene
Ruta
R
Fimmel
Sabine
S
Müller-Decker
Karin
K
Zouboulis
Christos C
CC
D000152:Acne Vulgaris / Q000201:enzymology* / Q000276:immunology; D000293:Adolescent; D000328:Adult; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis*; D004851:Epoxide Hydrolases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012627:Sebaceous Glands / Q000166:cytology / Q000201:enzymology* / Q000473:pathology
D015850:Interleukin-6; D016209:Interleukin-8; D008565:Membrane Proteins; D047492:Peroxisome Proliferator-Activated Receptors; D020033:Protein Isoforms; D007975:Leukotriene B4; D016718:Arachidonic Acid; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D004851:Epoxide Hydrolases; D015232:Dinoprostone; C043134:leukotriene A4 hydrolase