Hypothesis: from epidermal barrier dysfunction to atopic disorders

Taı̈eb, Alain

doi:10.1111/j.1600-0536.1999.tb06125.x

Cited by 136 publications

(105 citation statements)

References 32 publications

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“…Furthermore, colonization by superantigen-producing S aureus strains further exacerbates disease in patients with severe AD through generalized augmentation of IgE production, as well as through development of specific IgE directed toward staphylococcal exotoxins (see the "Impaired antimicrobial defense further compromises barrier function in AD" section below). 19 In addition, patients with AD are also susceptible to widespread cutaneous viral infections, including molluscum contagiosum, herpes simplex (Kaposi's varicelliform eruption), and lifethreatening vaccinia. 22 Widespread dermatophytosis (tinea corporis) and Malassezia species infections also occur in AD, and the latter, such as S aureus, can stimulate specific IgE production.…”

Section: Broad Barrier Failure In Admentioning

confidence: 99%

Basis for the barrier abnormality in atopic dermatitis: Outside-inside-outside pathogenic mechanisms

Elias

Hatano

Williams

2008

Journal of Allergy and Clinical Immunology

413

364

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Until quite recently, the pathogenesis of atopic dermatitis (AD) has been attributed to primary abnormalities of the immune system. Intensive study revealed the key roles played by T H 1/T H 2 cell dysregulation, IgE production, mast cell hyperactivity, and dendritic cell signaling in the evolution of the chronic, pruritic, inflammatory dermatosis that characterizes AD. Accordingly, current therapy has been largely directed toward ameliorating T H 2-mediated inflammation and pruritus. In this review we will assess emerging evidence that inflammation in AD results from inherited and acquired insults to the barrier and the therapeutic implications of this paradigm. KeywordsAntimicrobial peptides; atopic dermatitis; barrier function; barrier repair; cytokines; filaggrin; pH; psychologic stress; Staphylococcus aureus; serine proteases; T H 2 cells Until recently, atopic dermatitis (AD) has been viewed largely as a disease of immunologic etiology. 1-5 Yet, the epidermis generates a set of protective/defensive functions (Table I) mediated by its unique differentiation end product, the stratum corneum (SC). 6,7 These functions include the permeability barrier, which retards transcutaneous evaporative water loss, allowing survival in a potentially desiccating external environment, and an antimicrobial barrier, which simultaneously encourages colonization by nonpathogenic ''normal'' flora while resisting growth of microbial pathogens. 8 Although both a defective epidermal permeability 9-13 and a propensity to secondary infection 14,15 are well-recognized features of AD, these abnormalities have been widely assumed to reflect downstream consequences of a primary immunologic abnormality (the historical inside-outside view of AD pathogenesis). We and others have long proposed that the permeability barrier abnormality inADis not merely an epiphenomenon but rather the ''driver'' of disease activity (ie, the reverse outside-inside view of disease pathogenesis) 16-19 for the following reasons: (1) the extent of the permeability barrier abnormality parallels the severity of the disease phenotype in AD 9,10,12 ; (2) both clinically uninvolved skin sites and skin cleared of inflammation for as long as 5 years continue to display significant barrier abnormalities 10,13 ; (3) emollient therapy comprises effective ancillary therapy 20 ; and most importantly, (4) specific replacement therapy, which targets the NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript prominent lipid abnormalities that account for the barrier abnormality in AD (see below), corrects both the permeability barrier abnormality and comprises effective anti-inflammatory therapy for AD (see the Therapeutic implications section below). BROAD BARRIER FAILURE IN ADLike permeability barrier dysfunction, the antimicrobial barrier is also compromised in patients with AD. Colonization by Staphylococcus aureus is a common feature of AD, 21 and although colonization is highest on lesional skin, colony counts often are high on the clinically no...

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Section: Broad Barrier Failure In Admentioning

confidence: 99%

Basis for the barrier abnormality in atopic dermatitis: Outside-inside-outside pathogenic mechanisms

Elias

Hatano

Williams

2008

Journal of Allergy and Clinical Immunology

413

364

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“…While it has been previously assumed that these abnormalities reflect Th2-driven immunologic abnormalities (the historical 'inside-to-outside' view of AD pathogenesis), we and others have long proposed that the barrier abnormality is not merely a secondary phenomenon, but rather the 'driver' of disease activity in AD ('outside-to-inside' view of disease pathogenesis) [6][7][8] , because it was well-known that: 1) the extent of the permeability barrier abnormality parallels severity of disease phenotype in AD 1,2,4 ; 2)…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Implications of a Barrier-based Pathogenesis of Atopic Dermatitis

Elias

2010

Ann Dermatol

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In this review, I first provide relevant background information about normal epidermal barrier structure and function. I then update recent information about how inherited defects in either filaggrin and/or in the serine protease inhibitor, lymphoepithelial Kazal-type inhibitor 1, converge to stimulate the development of atopic dermatitis (AD). Next I explain the multiple mechanisms whereby a primary barrier abnormality in AD can lead to inflammation. Furthermore, I explore how certain acquired stressors, such as a reduced external humidity, high pH soaps/surfactants, psychological stress, as well as secondary Staphylococcus aureus infections initiate or further aggravate AD. Finally, and most importantly, I compare various therapeutic paradigms for AD, highlighting the risks and benefits of glucocorticoids and immunomodulators vs. corrective, lipid replacement therapy. (Ann Dermatol 22(3) 245∼254, 2010)

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“…이러한 분 화과정에서 각질형성세포는 납작한 모양의 핵이 없는 각질세 포로 변형되고, 동시에 표피의 과립층과 유극층 상부에서 인 볼루크린(involucrin) [14], 표피의 과립층과 각질층에서 로리 크린(loricrin), 필라그린(filaggrin) [24,48,50] 등 분화를 촉진 하는 인자들이 발현하여 [12,51] 각질 내 케라틴 세섬유 (keratin filament)를 응집함으로써 단단하고 편평한 구조인 각 질세포막(cornified cell envelope)을 형성, 피부의 강력한 물리 적인 장벽과 투과장벽기능에 기여하게 된다 [49]. 특히, filaggrin은 분해과정을 통해 pyrrocarboxylic acid나 trans-urocanic acid등의 천연함습인자(natural moisturizing factors) 를 형성하여 피부 보습에 중요한 역할을 수행함은 물론, 각질 층 pH의 정상화, 항염작용 등도 수행한다 [9,19].…”

Section: 서 론unclassified

The Effects of the Fruits of Foeniculum vulgare on Skin Barrier Function and Hyaluronic Acid Production in HaCaT Keratinocytes

유학인¹,

양인준²,

빅터루베리오린차³

et al. 2015

Journal of Life Science

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Foeniculum vulgare (FV) has long been used in traditional medicine for the treatment of inflammatory diseases. In addition, it is usually known as an important medicinal and aromatic plant widely used as a carminative, digestive, lactogogue, and diuretic, and for treating respiratory and gastrointestinal disorders. The skin barrier protects against the invasion of pathogens, fends off chemical and physical assaults, and protects against extensive water loss. In this study, the effects of solvent-fractionated FV fruits on strengthening the skin barrier and maintaining moisture, as well as their antifungal activity, were investigated in human keratinocyte (HaCaT) cells. The expression of involucrin, loricrin, filaggrin, hyaluronic acid synthase, human β defensin, and cathelicidin genes and proteins was measured by reverse transcription polymerase chain reaction (RT-PCR) and western blotting. The production of hyaluronic acid was determined by enzyme-linked immunosorbent assay (ELISA). The butanol fraction increased the expression of involucrin and filaggrin. Both the ethyl acetate and the butanol fractions increased hyaluronic acid production by promoting the expression of hyaluronic acid synthase-1. Although the antimicrobial peptides were increased by FV crude extract and its fractions, the samples did not show a significant effect compared to the normal group. These results suggest that the butanol fraction of FV could be very useful in cosmetics for the treatment of dermatological diseases.

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Hypothesis: from epidermal barrier dysfunction to atopic disorders

Cited by 136 publications

References 32 publications

Basis for the barrier abnormality in atopic dermatitis: Outside-inside-outside pathogenic mechanisms

Basis for the barrier abnormality in atopic dermatitis: Outside-inside-outside pathogenic mechanisms

Therapeutic Implications of a Barrier-based Pathogenesis of Atopic Dermatitis

The Effects of the Fruits of Foeniculum vulgare on Skin Barrier Function and Hyaluronic Acid Production in HaCaT Keratinocytes

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