Interferon-γ Decreases Ceramides with Long-Chain Fatty Acids: Possible Involvement in Atopic Dermatitis and Psoriasis

Ceramide (CER) with long-chain fatty acids (FAs) in the human stratum corneum (SC) is important for the skin barrier functions. Changes in the CER profile have been associated with abnormal permeability of dermatoses such as atopic dermatitis (AD) and psoriasis. In addition, interferon-γ (IFN-γ) has been known to be abundant in both AD and psoriatic skin lesions. In this study, we aimed to identify the mechanism underlying the alteration of FA chain length of CERs in these diseases. Mass spectrometry analysis of CERs in the SC showed that the proportion of CERs with long-chain FAs was significantly lower in AD and psoriasis patients than in healthy controls, and this reduction was more pronounced in psoriasis than in AD. Using cultured human keratinocytes and epidermal sheets, we found that only IFN-γ among various cytokines decreased the mRNA expression of elongase of long-chain fatty acids (ELOVL) and ceramide synthase (CerS), enzymes involved in FA chain elongation. Furthermore, quantitative analysis showed that IFN-γ decreased the levels of CERs with long-chain FAs. These results suggest that IFN-γ decreases CERs with long-chain FAs through the downregulation of ELOVL and CerS and that this mechanism may be involved in the CER profile alteration observed in psoriasis and AD

Vascular Endothelial Cell Injury Is an Important Factor in the Development of Encapsulating Peritoneal Sclerosis in Long-Term Peritoneal Dialysis Patients

<div><p>Background and Objectives</p><p>Encapsulating peritoneal sclerosis (EPS) is a rare but serious and life-threatening complication of peritoneal dialysis (PD). However, the precise pathogenesis remains unclear; in addition, predictors and early diagnostic biomarkers for EPS have not yet to be established.</p><p>Methods</p><p>Eighty-three peritoneal membrane samples taken at catheter removal were examined to identify pathological characteristics of chronic peritoneal deterioration, which promotes EPS in patients undergoing long-term PD treatment with low occurrence of peritonitis.</p><p>Results</p><p>According to univariable logistic regression analysis of the pathological findings, thickness of the peritoneal membrane (<i>P</i> = 0.045), new membrane formation score (<i>P</i> = 0.006), ratio of luminal diameter to vessel diameter (L/V ratio, <i>P</i><0.001), presence of CD31-negative vessels (<i>P</i> = 0.021), fibrin deposition (<i>P</i><0.001), and collagen volume fraction (<i>P</i> = 0.018) were associated with EPS development. In analyses of samples with and without EPS matched for PD treatment period, non-diabetes, and PD solution, univariable analysis identified L/V ratio (per 0.1 increase: odds ratio (OR) 0.44, <i>P</i> = 0.003) and fibrin deposition (OR 6.35, <i>P</i> = 0.027) as the factors associated with EPS. L/V ratio was lower in patients with fibrin exudation than in patients without fibrin exudation.</p><p>Conclusions</p><p>These findings suggest that damage to vascular endothelial cells, as represented by low L/V ratio, could be a predictive finding for the development of EPS, particularly in long-term PD patients unaffected by peritonitis.</p></div

Representative pathological findings of severe peritonitis, which is associated with fibrin exudation.

<p>Fungal peritonitis (<b>A</b>-<b>D</b>), <i>Pseudomonas aeruginosa</i> peritonitis (<b>E</b>, <b>F</b>), and <i>Serratia marcescens</i> peritonitis (<b>G, H</b>) show exudation of fibrin on the surface of peritoneal membrane associated with inflammatory cell infiltration. <b>B, D</b>, <b>F, and H</b> are serial sections of panels <b>A, C, E,</b> and <b>G</b>, respectively. <b>C</b> and <b>D</b> show higher-magnification images of the boxed areas in <b>A</b> and <b>B</b>. Black and blue arrows indicate the same areas in serial sections. <b>A</b>, <b>C</b>, <b>E</b>, and <b>G:</b> HE staining; <b>B</b>, <b>D</b>, <b>F,</b> and <b>H:</b> PTAH staining. Scale bars in <b>A</b> and <b>B</b> = 200 μm. Scale bars in <b>C</b> to <b>H</b> = 100 μm.</p

Differences in general characteristics and pathological findings between the EPS and non-EPS groups matched for PD treatment period, non-diabetes and PD solution (acidic or neutral pH).

<p>Differences in general characteristics and pathological findings between the EPS and non-EPS groups matched for PD treatment period, non-diabetes and PD solution (acidic or neutral pH).</p

General characteristics and pathological findings.

<p>General characteristics and pathological findings.</p

L/V ratio was lower in PD patients with fibrin exudation than in those without fibrin exudation.

<p>A, <b>cohort of</b> <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0154644#pone.0154644.t001" target="_blank">Table 1</a> <b>(n = 83),</b> B: <b>cohort of</b> <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0154644#pone.0154644.t003" target="_blank">Table 3</a> <b>(n = 30).</b></p

Collagen volume fraction (collagen density) in submesothelial compact zone is higher in the EPS development group than in non-EPS development group.

<p><b>A, B:</b> Picrosirius red stain, <b>C, D:</b> Collagen volume fraction (collagen density). <b>A, C:</b> non-EPS development group, <b>B, D:</b> EPS development group. <b>Scale bars = 200 μm.</b></p

Logistic regression analysis of clinical and pathological predictors for EPS.

<p>Logistic regression analysis of clinical and pathological predictors for EPS.</p

Pathological findings of peritoneal membrane taken at PD catheter removal for predicting EPS.

<p><b>A, B: Presence of new membrane formation.</b> Negative (<b>A</b>), positive (<b>B</b>). Arrows indicate new membrane formation. <b>C, D: Vasculopathy assessed by luminal diameter to vessel diameter (L/V) ratio at the level of the postcapillary venules.</b> (<b>C</b>) Mild vasculopathy (L/V ratio = 0.78). (<b>D</b>) Severe vasculopathy (arrows, L/V ratio = 0–0.14). <b>E, F: Presence of CD31-negative vessels.</b> Arrows indicate negative staining for CD31 (<b>F</b>) due to severe endothelial cell damage. <b>G, H: Fibrin deposition.</b> Fibrin deposition (arrows) was demonstrated by PTAH staining (<b>H</b>). <b>I, J: Peritoneal thickness.</b> Thickened peritoneum is prone to be high occurrence of EPS (<b>J</b>). <b>A, B, I,</b> and <b>J, HE staining; C, D</b> and <b>E,</b> Masson’s trichrome staining; <b>F,</b> CD31 immunostaining; <b>G, H,</b> PTAH staining. Scale bars in A, B, I, and J = 200 μm. Scale bars in C to H = 100 μm.</p