title: Pyrrolidone carboxylic acid levels or caspase-14 expression in the corneocytes of lesional skin correlates with clinical severity, skin barrier function and lesional inflammation in atopic dermatitis.
abstract: BACKGROUND
  Dry skin in atopic dermatitis (AD) mainly results from barrier impairment due to deficiency of ceramide and natural moisturizing factors including pyrrolidone carboxylic acid (PCA) in stratum corneum (SC). Caspase-14 cleaves filaggrin monomers to free amino acids and their derivatives such as PCA, contributing natural moisturizing factors. Cytokines in the corneocytes represent cutaneous inflammation severity of AD patients.
  
  
  OBJECTIVE
  To analyze the correlations of PCA, caspase-14 and cytokines in corneocytes with clinical severity, barrier function and skin inflammation, those were quantitated.
  
  
  METHODS
  A total of 73 persons were enrolled: 21 patients with mild AD, 21 with moderate-to-severe AD, 13 with X-linked ichthyosis (XLI) as a negative control for filaggrin gene (FLG) mutation, and 18 healthy controls. Skin barrier functions such as basal transepidermal water loss (TEWL), stratum corneum (SC) hydration and skin surface pH were measured. To collect corneocytes, stripping with D-squame discs was done on lesional and non-lesional skin. And then PCA was isolated from D-squame discs and quantitated by LC-MS/MS. Cytokine assays were performed.
  
  
  RESULTS
  The quantity of PCA and caspase-14 was decreased in inflammatory lesions compared to non-lesion in AD patients. And the amounts of PCA and caspase-14 in the lesion of AD patients correlated with clinical severity as determined by eczema area and severity index score and the skin barrier functions. Also, the expressions of TNF-α and IL-13 inversely correlated with PCA quantity.
  
  
  CONCLUSIONS
  The quantity of PCA or caspase-14 in the corneocytes of the lesional skin of AD patients reflects the clinical severity, skin barrier function and the degree of lesional inflammation.
authors.affiliation: Department of Dermatology, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju, 220-701 Korea.
authors.forename: Minyoung
authors.initials: M
authors.lastname: Jung
authors.affiliation: Department of Dermatology, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju, 220-701 Korea.
authors.forename: Jaewoong
authors.initials: J
authors.lastname: Choi
authors.affiliation: Seoul Medical Center Research Institute, Seoul, Korea.
authors.forename: Seon-Ah
authors.initials: SA
authors.lastname: Lee
authors.affiliation: Seoul Medical Center Research Institute, Seoul, Korea; Atopy Asthma Center/Department of Dermatology, Seoul Medical Center, Seoul, Korea.
authors.forename: Hyunjung
authors.initials: H
authors.lastname: Kim
authors.affiliation: WCI Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Korea.
authors.forename: Joonsung
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Department of Dermatology, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju, 220-701 Korea. Electronic address: choieh@yonsei.ac.kr.
authors.forename: Eung Ho
authors.initials: EH
authors.lastname: Choi
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D020169:Caspases / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D016114:Ichthyosis, X-Linked / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018793:Interleukin-13 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000235:genetics; D008297:Male; D009154:Mutation; D011761:Pyrrolidonecarboxylic Acid / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; C578095:IL13 protein, human; D018793:Interleukin-13; D053583:Interleukin-1beta; D007381:Intermediate Filament Proteins; D014409:Tumor Necrosis Factor-alpha; C506446:CASP14 protein, human; D020169:Caspases; D011761:Pyrrolidonecarboxylic Acid
keywords: Atopic dermatitis; Caspase-14; Filaggrin; Natural moisturizing factor; Pyrrolidone carboxylic acid