Zileuton prevents the activation of the leukotriene pathway and reduces sebaceous lipogenesis.
Arachidonic acid (AA) activates the 5-lipoxygenase, induces leukotriene-B(4) (LTB(4)) synthesis, enhances interleukin-6 (IL-6) release and increases intracellular neutral lipids in human sebocytes. Moreover, the enzymes of LTB(4) biosynthesis are activated in acne-involved sebaceous glands. Zileuton a 5-lipoxygenase inhibitor, reduces the number of inflammatory acne lesions and lipogenesis in patients with acne. In this study, we investigated the activity of zileuton on LTB(4) generation, lipid content and IL-6 and -8 release from human SZ95 sebocytes in vitro. Pretreatment with zileuton partially prevented the AA-induced LTB(4) and IL-6 release and increased neutral lipid content. IL-6 release and neutral lipid content were also reduced under long-term zileuton treatment. In conclusion, zileuton prevents the activation of the leukotriene pathway and enhancement of lipogenesis by AA in human sebocytes in vitro.
Zouboulis
Christos C
CC
Seltmann
Holger
H
Alestas
Theodosios
T
D016718:Arachidonic Acid / Q000633:toxicity; D002452:Cell Count; D002460:Cell Line; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000378:metabolism*; D050155:Lipogenesis / Q000187:drug effects*; D012627:Sebaceous Glands / Q000187:drug effects* / Q000378:metabolism
D015850:Interleukin-6; D016209:Interleukin-8; D020024:Leukotriene Antagonists; D007975:Leukotriene B4; D016718:Arachidonic Acid; C063449:zileuton; D006918:Hydroxyurea