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Review
. 2014 Mar;1841(3):323-30.
doi: 10.1016/j.bbalip.2013.10.001. Epub 2013 Oct 12.

Lipid abnormalities and lipid-based repair strategies in atopic dermatitis

Peter M Elias  1
Affiliations
Review

Lipid abnormalities and lipid-based repair strategies in atopic dermatitis

Peter M Elias. Biochim Biophys Acta. 2014 Mar.

Abstract

Prior studies have revealed the key roles played by Th1/Th2 cell dysregulation, IgE production, mast cell hyperactivity, and dendritic cell signaling in the evolution of the chronic, pruritic, inflammatory dermatosis that characterizes atopic dermatitis (AD). We review here increasing evidence that the inflammation in AD results primarily from inherited abnormalities in epidermal structural and enzymatic proteins that impact permeability barrier function. We also will show that the barrier defect can be attributed to a paracellular abnormality due to a variety of abnormalities in lipid composition, transport and extracellular organization. Accordingly, we also review the therapeutic implications of this emerging pathogenic paradigm, including several current and potentially novel, lipid-based approaches to corrective therapy. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.

Keywords: Antimicrobial peptide; Atopic dermatitis; Barrier function; Filaggrin; Serine protease inhibitor; pH.

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Figures

Fig. 1
Fig. 1
‘OUTSIDE-INSIDE’ HOMEOSTATIC RESPONSES CAN ALSO PROVOKE A CYTOKINE CASCADE LEADING TO INFLAMMATION
Fig. 2
Fig. 2
How Filaggrin Deficiency Predisposes to Atopic Dermatitis Trans-urocanic acid (t-UCA) is the most potent endogenous UV-B filter in lightlypigmented skin. Loss of t-UCA could account for the higher incidence of nonmelanoma skin cancers in AD. (Elias, P. & Williams, M. J Invest Dermatol. 133(6): 1,676–1,677, 2013.)
Fig. 3
Fig. 3
Lessons from Netherton Syndrome: Central Role of KLKs
Fig. 4
Fig. 4
Lipid Metabolic Events Leading to Barrier Formation (Italics indicate abnormalities in atopic dermatitis) Abbreviations: β-Glccer’ase, β-glucocerebrosidase; aSMase, acidic sphingomyelinase; FATPs, fatty acid transport proteins; SSase, steroid sulfate; sPLA2, secretory phospholipase A2
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References

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