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Mucocutaneous Lesions of Behcet's Disease
Erkan Alpsoy,Christos Constantin Zouboulis,George Edward Ehrlich 연세대학교의과대학 2007 Yonsei medical journal Vol.48 No.4
Behcet's disease is particularly prevalent in “Silk Route” populations, but it has a global distribution. The diagnosis of the disease is based on clinical criteria as there is as yet no pathognomonic test, and mucocutaneous lesions, which figure prominently in the presentation and diagnosis, may be considered the diagnostic hallmarks. Among the internationally accepted criteria, painful oral and genital ulcers, cutaneous vasculitic lesions and reactivity of the skin to needle prick or injection (the pathergy reaction) are considered hallmarks of Behcet's disease, and often precede other manifestations. Their recognition may permit earlier diagnosis and treatment, with salutary results. This paper describes the various lesions that constitute the syndrome and focuses on those that may be considered characteristic.
LXRα Enhances Lipid Synthesis in SZ95 Sebocytes
Hong, Il,Lee, Min-Ho,Na, Tae-Young,Zouboulis, Christos C,Lee, Mi-Ock The Society for Investigative Dermatology, Inc 2008 The Journal of investigative dermatology Vol.128 No.5
Differentiation of sebocytes is strongly associated with enhanced lipid synthesis and accumulation in the cells. Liver X receptors (LXRs) are members of the nuclear receptor superfamily, which play a critical role in cholesterol homeostasis and lipid metabolism. We examined whether LXRα regulated lipid synthesis in the immortalized human sebaceous gland cell line SZ95. When the SZ95 sebocytes were treated with the ligand of LXR such as TO901317 or 22(R)-hydroxycholesterol, lipid droplets were accumulated in the majority of cells when examined by Oil Red O staining. The expression of the known LXR targets, such as fatty acid synthase and sterol regulatory-binding protein-1, was induced by TO901317. TO901317 treatment increased expression of LXRα but not that of LXRβ. Transfection of antisense LXRα significantly decreased TO901317-induced target gene expression and lipid droplet accumulation, suggesting a major role of LXRα in differentiation of sebocytes. Further, TO901317 decreased the expression of cyclooxygenase-2 and inducible nitric oxide synthase that was induced by lipopolysaccharide treatment. Together, these results indicate that important roles of LXRα in differentiation and inflammatory signaling in sebaceous glands. Thus, we suggest that LXR ligands could provide a new class of therapeutic agents for sebaceous gland-associated disorders such as seborrhea and acne.Journal of Investigative Dermatology (2008) 128, 1266–1272; doi:10.1038/sj.jid.5701134; published online 25 October 2007
Kim, So Young,Hyun, Moo Yeol,Go, Kyung Chan,Zouboulis, Christos C,Kim, Beom Joon UNKNOWN 2015 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.35 No.4
<P>Resveratrol is known to be a naturally produced polyphenol that is able to reduce cell proliferation in several types of cancer cells and adipocytes. However, the antiproliferative effects of resveratrol on the growth of human sebocytes are not yet clear. In the present study, we investigated possible cellular pathways associated with these growth inhibitory effects on human SZ95 sebocytes. Our results revealed that resveratrol inhibited the proliferation of sebocytes, and that this resulted in disruption of the cell cycle. The inactivation of extracellular signal-regulated protein kinase (ERK), Akt and peroxisome proliferator-activated receptor (PPAR)-γ was also shown to be involved in the inhibition of sebocyte growth by resveratrol. To examine the antiproliferative effects of resveratrol, we determined the levels of cell cycle control proteins. Resveratrol inhibited cyclin D1 synthesis, whereas it stimulated p21WAF1/CIP1 (p21) and p27KIP1 (p27) synthesis. In addition, we demonstrated that the resveratrol-mediated cell cycle arrest resulted in an increase in the proportion of cells in the sub-G0/G1 phase. Moreover, we found that the growth inhibitory effects of resveratrol were enhanced by treatment with LY294002 [a phosphatidylinositol 3-kinase (PI3-K) inhibitor] more so than by treatment with PD98059 (a MEK inhibitor), which indicates that resveratrol exerts its inhibitory effects on sebocyte proliferation through the inhibition of Akt. Linoleic acid (LA) is a well-established lipid inducer in sebocytes and is known to stimulate sebocyte differentiation through the upregulation of PPAR-γ. In this study, resveratrol was found to decrease the lipid content and PPAR-γ expression during LA-stimulated lipogenesis. Our results indicate that resveratrol plays a critical role in the inhibition of sebocyte growth through the inactivation of the Akt pathway. The present data suggest that resveratrol may be used as a therapeutic agent for the treatment of acne vulgaris.</P>
Autophagy regulates lipid production in human sebocytes
( Seong Hoon Seo ),( Ju Yeon Jung ),( Keedon Park ),( Christos C ),( Zouboulis ),( Sang Eun Lee ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.2
Background: Recently, lipids have been demonstrated to be targets for autophagosomal degradation in liver and adipose tissue. However, the function of autophagy in sebaceous glands is not yet fully understood. Objectives: To investigate the role of autophagy in sebaceous lipogenesis. Methods: SZ95 sebocytes were treated with either autophagy inhibitors or inducer, rapamycin with lipogenic stimuli. Intracellular lipids were assessed by BODIPY and fluorescent Nile Red staining. Autophagic activity was assessed by immunofluorescence and Western blot for autophagy markers. Autophagy markers expression in sebaceous gland was detected by immunohistochemistry. Results: In healthy human sebaceous glands, LC3B shows the strongest expression in the maturing sebocytes, but in acne lesional skin, LC3B expression is markedly reduced. IGF-1 or testosterone/linoleic acid inhibited starvationinduced sebocyte autophagy. Autophagy inhibitors led to increased lipid accumulation in sebocytes. Conversely, rapamycin inhibits the lipogenic actions of IGF-1 and testosterone/linoleic acid. All-trans retinoic acid (ATRA) increases autophagy markers in sebocytes, while autophagy inhibitors abolish the sebosuppressive effect of ATRA. Conclusion: Androgen and IGF-1 may contribute to reduce autophagic activity in sebocyte in acne. Autophagy plays an important role in the modulation of lipogenesis in human sebocytes and is responsible for the action of ATRA on sebostatic effect, thereby influencing the pathogenesis of acne
( Chao Hsuan Chen ),( Yan Han Wang ),( Teruaki Nakatsuji ),( Yu Tsueng Liu ),( Christos C. Zouboulis ),( Richard L. Gallo ),( Liangfang Zhang ),( Ming Fa Hsieh ),( Chun Ming Huang ) 한국미생물 · 생명공학회 2011 Journal of microbiology and biotechnology Vol.21 No.4
Free fatty acids (FFAs) are known to have bacteriocidal activity and are important components of the innateimmune system. Many FFAs are naturally present in human and animal skin, breast milk, and in the bloodstream. Here, the therapeutic potential of FFAs against methicillin-resistant Staphylococcus aureus (MRSA) is demonstrated in cultures and in mice. Among a series of FFAs, only oleic acid (OA) (C18:1, cis-9) can effectively eliminate Staphylococcus aureus (S. aureus) through cell wall disruption. Lauric acid (LA, C12:0) and palmitic acid (PA, C16:0) do not have this ability. OA can inhibit growth of a number of Gram-positive bacteria, including hospital and community-associated MRSA at a dose that did not show any toxicity to human sebocytes. The bacteriocidal activities of FFAs were also demonstrated in vivo through injection of OA into mouse skin lesions previously infected with a strain of MRSA. In conclusion, our results suggest a promising therapeutic approach against MRSA through boosting the bacteriocidal activities of native FFAs, which may have been co-evolved during the interactions between microbes and their hosts.
Effects of α‐melanocyte‐stimulating hormone on calcium concentration in SZ95 sebocytes
Whang, Sung Won,Lee, Sang Eun,Kim, Ji Min,Kim, Hyun Jung,Jeong, Se Kyoo,Zouboulis, Christos C.,Seo, Jeong Taek,Lee, Seung Hun Blackwell Publishing Ltd 2011 Experimental dermatology Vol.20 No.1
<P><B>Abstract: </B> Melanocortins have been implicated in human sebum secretion for a long time. However, the signalling pathways of α‐melanocyte‐stimulating hormone (α‐MSH) in human sebocytes expressing melanocortin receptors (MC‐Rs) are still poorly understood. Because calcium ions play a central role in MC‐R signalling, we investigated whether α‐MSH affects calcium signalling in the immortalized human sebocyte cell line SZ95. In addition, we investigated the impact of α‐MSH on MC‐1R expression and lipid synthesis in these cells. α‐MSH increased intracellular calcium levels. α‐MSH‐mediated calcium mobilization originated from intracellular calcium stores and was mediated by inositol triphosphate. Moreover, α‐MSH increased MC‐1R immunoreactivity and lipid synthesis in SZ95 sebocytes in the presence of testosterone. Our data demonstrate that α‐MSH in human sebocytes controls a key cellular signalling pathway, the calcium ion response, which may coordinate MC‐1R‐mediated sebum secretion.</P>