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

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 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.

An update on the role of the sebaceous gland in the pathogenesis of acne

“…PPARα is the most important PPAR that regulates lipid synthesis and inflammation. 40,41 In addition, PPAR-α, -δ, -γ1 and -γ2 have been shown to be expressed at mRNA and protein levels in SZ95 sebocytes. 39 Dehydroepiandrosterone (DHEA) has been also shown to regulate sebum production especially in postmenopausal women.…”

“…These molecules are synthesised from arachidonic acid (AA) or linolenic acid by the enzymes lipoxygenase (LOX) and cyclooxygenase (COX), respectively. Both COX isozymes, COX-1 and COX-2, are expressed in human sebocytes in vitro, in particular COX-2 expression is selectively upregulated in acne involved sebaceous glands in vivo 41 ( Fig. 4).…”

“…Treatment of SZ95 sebocytes with AA stimulates 5-LOX expression and induces LTB 4 synthesis. 41 In addition, AA induces the expression of the IL-6 and IL-8 cytokines. 5-LOX and LTA 4 hydrolase show a stronger expression in acne lesions than in normal skin and in uninvolved skin of acne patients.…”

“…5-LOX and LTA 4 hydrolase show a stronger expression in acne lesions than in normal skin and in uninvolved skin of acne patients. 41 The involvement of 5-LOX in the pathogenesis of acne has led to new therapeutic strategies to deal with the disease. 83 Cytokines are present in normal sebaceous glands, and they are affected by many factors.…”

“…IL-1α, TNFα, IL-6 and IL-8 are released into supernatant in unstressed sebocyte culture. 41 In a stressed environment, the amounts of released cytokines increase significantly. AA and calcium ionophore enhance the level of IL-6 and IL-8, but that of IL-1β and TNFα is not affected.…”