The effect of human sebum on skin barrier and its role in the pathogenesis of seborrheic dermatitis

  • 郭 俊文

Student thesis: Doctoral Thesis


Seborrheic dermatitis (SD) is a common recurrent chronic inflammatory skin disorder It generally arises in areas with high density of sebaceous glands Human sebum is a complex mixture of lipids which is secreted by mammalian sebaceous glands associated with hair follicles and forms a fluid film over the skin surface The functions of sebum have been known to soften the skin to regulate the water content of the epidermis to inhibit the growth of gram-positive bacteria and to prevent an invasion of external organisms It was hypothesized that the Malassezia yeasts consumed the saturated fatty acids released from the triglycerides and left behind the unsaturated fatty acids which cause inflammation and irritation However up to the present there is only very limited information about the effect of sebum on skin barrier and its role in the pathogenesis of SD Two studies were designed to clarify the sebum effect on skin barrier and its role in pathogenesis in SD In the first study using a hairless mouse model we clearly demonstrated the human sebum imparts detrimental effects on the skin permeability barrier both functionally and morphologically The underlying mechanisms for sebum-induced barrier disruption are related directly to the interaction of sebum with the intracellular lipid lamellae of the stratum corneum (SC) thereby leading to increase the fluidity of SC intracellular lipids as demonstrated by ATR-FTIR spectroscopic measurement Direct observation of the SC lipids by ruthenium tetroxide staining under electron microscope further confirm that intercellular lipid lamellae disorganization was the earliest morphological event following sebum application The disruption of the skin barrier elicit an epidermal inflammatory cascade with the release of IL-1? TNF-? and IL-6 from the keratinocytes and later inflammatory cells infiltration in the upper epidermis Although acute increase of these cytokines is crucial for skin barrier repair in chronic barrier disruption these cytokines cascade could have a harmful effect leading to cutaneous chronic inflammation Supported by the epidermal TSLP staining and serum IgE data and also in agreement with previous reports we may conclude that sebum-induced dermatitis resembles irritant contact dermatitis rather than allergic dermatitis In the second study we reported the first human study to demonstrate elevated levels of oleic acid in both the SD sebum and in the control sebum collected 72 hr versus 24 hr post hair washing Moreover chronic applications of SD sebum and modified control sebum with similar oleic acid content onto mouse skin resulted in a higher TEWL value than application of control sebum These results indicated possible involvement of C18 unsaturated fatty acid and possibly others in the pathogenesis of SD In summary results from both studies in concert identified possible relationships between sebum irritant contact dermatitis and SD These findings may have therapeutic implications for the treatment of SD
Date of Award2014 Aug 2
Original languageEnglish
SupervisorJui-Chen Tsai (Supervisor)

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