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

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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-α, but not receptor-γ1 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.

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Acknowledgements

Ruta Ganceviciene is a scholarship holder of the Berlin Foundation for Dermatology. We thank the group of Prof. W. Wahli (Center for Integrative Genomics, Lausanne, Switzerland) for the quantification of PPAR mRNA in the sebocyte samples. We are grateful to Dr. S. Pattabhiraman, Mr. H. Seltmann and Mr. A. Hossini for friendly advice and support and to Mrs. E. Glass for excellent technical assistance.

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Correspondence to Christos C. Zouboulis.

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

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Alestas, T., Ganceviciene, R., Fimmel, S. et al. Enzymes involved in the biosynthesis of leukotriene B4 and prostaglandin E2 are active in sebaceous glands. J Mol Med 84, 75–87 (2006). https://doi.org/10.1007/s00109-005-0715-8

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  • DOI: https://doi.org/10.1007/s00109-005-0715-8

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