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.
Acne is the most common skin disease which affects millions of people worldwide. Seborrhea and sebostasis are major cosmetic problems but also lead occasionally to diseases. This article summarizes the data of newest research of sebostasis, seborrhoea and acne made possible through the development of human and animal sebocyte culture models.
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 AAinduced 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.
UV-exposition is considered as the main reason for the development of cancers of the skin. However, 90 to 100% of the Vitamin-D reqirement is formed within the skin through the action of sunlight. Considering the results of epidemiological studies, that have detected an association of Vitamin-D deficiency with various types of cancer (e.g. colon-, prostate-and breast cancer), this is a real dilema. The cancer protective effect of vitamin-D is contributed to the extra renal, local production of 1a,25(OH) 2 D 3 by the 25-hydroxyvitamin D-1a-hydroxylase, which has been detected in various tissues. In respect of the novel functions of vitamin-D and the risk of adverse consequences in case of deficiency we have screened sun deprived risk groups (A: patients with genodermatoses connected with defects in sun-induced DNA repair: n ¼ 4: 3 patients with xeroderma pigmentosum and 1 patient with basal cell nevus syndrome; and B: non vitamin-D substituted renal transplant recipients under immunosuppressants: n ¼ 33) for their vitamin-D status. As measure of the vitamin-D store and as substrate for the 25-hydroxyvitamin D-1a-hydroxylase basal 25(OH)D 3 serum levels (Nichols Institute Diagnostika GmbH, Bad Nauheim, Germany) have been analysed. In both groups decreased basal 25(OH)D 3 serum levels were detected. Therefore we demand a monitoring of vitamin-D status in patients practising sun protection, in case of vitamin-D deficiency an oral substitution should be recommended.Effect of UVB radiation emitted from the narrowband TL-01 lamp (311 nm) on the calcitriol synthesis in organotypic cultures of keratinocytesThe skin is the only tissue yet known in which the complete UVB-induced pathway from 7-dehydrocholesterol (7-DHC) to hormonally active calcitriol (1a,25-dihydroxyvitamin D 3 ) occurs under physiological conditions. It is well known that both calcitriol and UVB radiation exert potent antipsoriatic effects. We speculate that the therapeutic effect of UVB radiation can be
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