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. 2008 Mar;126(3):332-7.
doi: 10.1016/j.clim.2007.11.006. Epub 2007 Dec 31.

Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6

Byung Eui Kim  1 , Donald Y M Leung, Mark Boguniewicz, Michael D Howell
Affiliations

Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6

Byung Eui Kim et al. Clin Immunol. 2008 Mar.

Abstract

Atopic dermatitis (AD) is characterized by a defective skin barrier which allows increased allergen and pathogen penetration. Loricrin (LOR) and involucrin (IVL) are proteins important for skin barrier formation and integrity. In this study, we demonstrate that the gene and protein expression of LOR and IVL is significantly decreased in involved (LOR: p<0.001; IVL: p<0.001) and uninvolved (LOR: p<0.001; IVL: p<0.001) skin of AD subjects, as compared to skin from healthy subjects. Using primary keratinocytes, we further demonstrate the down-regulatory effect of IL-4 and IL-13--which are over-expressed in the skin of AD patients--on LOR and IVL expression in keratinocytes. Additionally, skin biopsies from signal transducer and activator of transcription (STAT)-6 transgenic mice were deficient in the expression and production of LOR and IVL. This study suggests that Th2 cytokines inhibit expression of LOR and IVL through a STAT-6 dependent mechanism.

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Figures

Figure 1
Figure 1
Gene expression of LOR and IVL in skin from normal subjects and AD patients. RNA was isolated from the skin of 13 normal subjects and 14 patients with AD, and the gene levels of LOR (A) and IVL (B) were evaluated by real-time RT-PCR. *P < 0.05; **P < 0.01; ***P < 0.001.
Figure 1
Figure 1
Gene expression of LOR and IVL in skin from normal subjects and AD patients. RNA was isolated from the skin of 13 normal subjects and 14 patients with AD, and the gene levels of LOR (A) and IVL (B) were evaluated by real-time RT-PCR. *P < 0.05; **P < 0.01; ***P < 0.001.
Figure 2
Figure 2
Decreased LOR and IVL staining in AD skin. (A, B) Representative paraffin embedded skin biopsies from normal subjects (n = 13), and patients with AD (n = 14) stained for LOR (A) and IVL (B) are shown. Images were collected at ×400 magnification. (C, D) The intensities of the staining for LOR (C) and IVL (D) were graded visually on a scale from 0 (no staining) to 5 (the most intense staining). *P < 0.05; **P < 0.01; ***P < 0.001.
Figure 2
Figure 2
Decreased LOR and IVL staining in AD skin. (A, B) Representative paraffin embedded skin biopsies from normal subjects (n = 13), and patients with AD (n = 14) stained for LOR (A) and IVL (B) are shown. Images were collected at ×400 magnification. (C, D) The intensities of the staining for LOR (C) and IVL (D) were graded visually on a scale from 0 (no staining) to 5 (the most intense staining). *P < 0.05; **P < 0.01; ***P < 0.001.
Figure 2
Figure 2
Decreased LOR and IVL staining in AD skin. (A, B) Representative paraffin embedded skin biopsies from normal subjects (n = 13), and patients with AD (n = 14) stained for LOR (A) and IVL (B) are shown. Images were collected at ×400 magnification. (C, D) The intensities of the staining for LOR (C) and IVL (D) were graded visually on a scale from 0 (no staining) to 5 (the most intense staining). *P < 0.05; **P < 0.01; ***P < 0.001.
Figure 2
Figure 2
Decreased LOR and IVL staining in AD skin. (A, B) Representative paraffin embedded skin biopsies from normal subjects (n = 13), and patients with AD (n = 14) stained for LOR (A) and IVL (B) are shown. Images were collected at ×400 magnification. (C, D) The intensities of the staining for LOR (C) and IVL (D) were graded visually on a scale from 0 (no staining) to 5 (the most intense staining). *P < 0.05; **P < 0.01; ***P < 0.001.
Figure 3
Figure 3
Th2 cytokines down-regulate the gene expressions of LOR and IVL. Primary human keratinocytes were differentiated in the absence and presence of IL-4, IL-13 or combination of IL-4 and IL-13 for 5 days. Then RNA was isolated from the cells, and the gene expressions of LOR (A) and IVL (B) were examined by real-time RT-PCR. ***P < 0.001.
Figure 3
Figure 3
Th2 cytokines down-regulate the gene expressions of LOR and IVL. Primary human keratinocytes were differentiated in the absence and presence of IL-4, IL-13 or combination of IL-4 and IL-13 for 5 days. Then RNA was isolated from the cells, and the gene expressions of LOR (A) and IVL (B) were examined by real-time RT-PCR. ***P < 0.001.
Figure 4
Figure 4
Gene expression of LOR and IVL was decreased in STAT-6 transgenic mice. Skin biopsies were obtained from 15 wild type (C57BL/6) and 15 STAT-6 transgenic mice, and gene expression of LOR (A) and IVL (B) was evaluated using real-time RT-PCR.
Figure 4
Figure 4
Gene expression of LOR and IVL was decreased in STAT-6 transgenic mice. Skin biopsies were obtained from 15 wild type (C57BL/6) and 15 STAT-6 transgenic mice, and gene expression of LOR (A) and IVL (B) was evaluated using real-time RT-PCR.
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