Eung-Ho Choi

Psychological stress downregulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections in mice

The skin is the first line of defense against microbial infection, and psychological stress (PS) has been shown to have adverse effects on cutaneous barrier function. Here we show that PS increased the severity of group A Streptococcus pyogenes (GAS) cutaneous skin infection in mice; this was accompanied by increased production of endogenous glucocorticoids (GCs), which inhibited epidermal lipid synthesis and decreased lamellar body (LB) secretion. LBs encapsulate antimicrobial peptides (AMPs), and PS or systemic or topical GC administration downregulated epidermal expression of murine AMPs cathelin-related AMP and beta-defensin 3. Pharmacological blockade of the stress hormone corticotrophin-releasing factor or of peripheral GC action, as well as topical administration of physiologic lipids, normalized epidermal AMP levels and delivery to LBs and decreased the severity of GAS infection during PS. Our results show that PS decreases the levels of 2 key AMPs in the epidermis and their delivery into LBs and that this is attributable to increased endogenous GC production. These data suggest that GC blockade and/or topical lipid administration could normalize cutaneous antimicrobial defense during PS or GC increase. We believe this to be the first mechanistic link between PS and increased susceptibility to infection by microbial pathogens.

Enhancement of optical skin clearing efficacy using a microneedle roller

Light scattering in biological tissues can be reduced by using optical clearing agents. Various physical methods in conjunction with agents have been studied to enhance the optical clearing efficacy of skin for diagnostic and therapeutic applications. In this study, we propose a new physical method to enhance the optical clearing potential of topically applied glycerol. A microneedle roller is used to easily create numerous transdermal microchannels prior to glycerol application. The optical clearing efficacy of skin is quantitatively evaluated with the use of a modulation transfer function target placed underneath ex vivo porcine skin samples. From cross-polarized images acquired at various time points after glycerol application, we find that samples treated with the microneedle roller resulted in an approximately two-fold increase in contrast compared to control samples 30 min after glycerol application. In conclusion, our data suggest that the microneedle roller can be a good physical method to enhance transdermal delivery of optical clearing agents, and hence their optical clearing potential over large regions of skin.

Topical calcineurin inhibitors compromise stratum corneum integrity, epidermal permeability and antimicrobial barrier function.

Please cite this paper as: Topical calcineurin inhibitors compromise stratum corneum integrity, epidermal permeability and antimicrobial barrier function. Experimental Dermatology 2010; 19: 501–510.

Activators of PPARs and LXR decrease the adverse effects of exogenous glucocorticoids on the epidermis.

Abstract:  While glucocorticoids (GC) exert beneficial effects (anti‐inflammatory), they also have adverse effects on the epidermis including decreased epidermal differentiation, decreased keratinocyte proliferation, and decreased cutaneous permeability barrier homeostasis. Thus, the purpose of this study was to develop strategies to prevent these GC toxicities using simultaneous topical treatments in clobetasol‐treated mice. While a triple‐lipid mixture of stratum corneum lipids (ceramide, free fatty acid and cholesterol) was previously shown to reverse the GC‐induced abnormality in cutaneous barrier function [J Invest Dermatol, 120 (2003) 456], this lipid mixture did not prevent the GC‐induced abnormalities in either keratinocyte proliferation or differentiation. As activators of PPARα, β/δ, γ and LXR, regulate keratinocyte proliferation and differentiation and improve permeability barrier homeostasis, we next assessed the effects of these activators during concurrent GC treatment. Co‐application of either ciglitazone (PPARγ activator), clofibrate (PPARα activator) or 22R (OH) cholesterol (LXR activator) with clobetasol prevented the decrease in involucrin, filaggrin and loricrin expression. By contrast, a PPARβ/δ activator (GW501516) normalized only the expression of involucrin and filaggrin but not loricrin. Moreover, topical application of PPARα, β/δ or LXR activators partially prevented the decrease in keratinocyte proliferation in GC‐treated murine skin, as measured using PCNA, while no effect was seen after co‐treatment with PPARγ activators. Finally, PPARγ and PPARβ/δ activators but not PPARα and LXR activators improved permeability barrier homeostasis in GC‐treated mice. Together, these studies demonstrate that PPAR and LXR activators can prevent several of the adverse effects of topical GC on the epidermis.

Antinuclear antibodies in patients with prurigo pigmentosa: a linkage or a coincidence?

Laboratory tests were within normal limits except for elevated ANA (1: 320, homogenous pattern), IgE ( 1 1,000 IU/ml) and eosinophil count (760 ! 10 6 /l). Other laboratory findings related to autoimmunity [anti-SS-A(Ro), anti-SS-A(La), ds-DNA antibodies] were negative. A skin biopsy showed marked spongiosis, exocytosis of neutrophils, blurring of dermoepidermal junctions, and superficial perivascular and interstitial lymphocytic infiltration ( fig. 2 a). Direct immunofluorescences (DIFs) were all negative. All of the features were consistent with PP. Daily treatment with 100 mg of doxycycline and 50 mg of dapsone was started. After 2 weeks, almost all of the lesions had been resolved leaving hyperpigmentation. The second patient was a 15-year-old female who presented with a 3-week history of a pruritic, erythematous eruption in the intermammary region and on the back ( fig. 1 b). She had been intermittently treated with topical corticosteroids for atopic dermatitis. Laboratory findings showed elevated ANA (1: 320, speckled pattern) and IgE (934 IU/ml). Additional laboratory findings related to autoimmunity [anti-SS-A(Ro), anti-SS-A(La), ds-DNA, anti-Sm antibodies] were negative. Histopathologic features showed intraepidermal blister, spongiosis, marked exocytosis, vacuolar alteration at the dermoepidermal junction and superficial perivascular lymphocytic infiltration ( fig. 2 b). DIFs were all negative. After the diagnosis of PP, treatment with 8 mg of methylprednisolone and 0.05% desonide lotion induced a dramatic response. The last patient was a 16-year-old female with a 3-week history of pruritic vesicular skin lesion on her back ( fig. 1 c). We performed a Tzanck smear from vesicular lesions, but it was negative. Laboratory findings showed elevated ANA (1: 80, homogenous pattern) and IgE (139 IU/ml), and other laboratory findings including autoimmunity [anti-SS-A(Ro), anti-SS-A(La), ds-DNA, anti-Sm antibodies] were within normal limits or negative. Histopathologic features were consistent with PP ( fig. 2 c), and DIFs were all negative. She was treated with 20 mg of prednisolone and

Increased retinol-binding protein (RBP) 4 and anti-RBP4 antibody in alopecia areata.

Background  Neither the underlying pathogenesis of alopecia areata (AA) nor the molecular mechanisms leading to hair loss have been fully elucidated.

Effect of lacquering on indoor air carbonyl compound quality and human malondialdehyde levels

Formaldehyde and other organic compounds are known to provoke allergy including asthma and atopid dermatitis by producing IgE antibody when the aldehyde is combined with various proteins in the body such as albumin. To determine if lacquering could reduce the allergic effects of various environmental pollutants, we measured indoor air quality improvement and examined urinary malondialdehyde (MDA) concentration to provide basic data on the use of lacquering as a means of indoor air quality management. Results showed that formaldehyde, acetaldehyde, acetone and benzaldehyde levels before lacquering were found to be 33.25–194.30, 2.24–47.55, 23.78–146.20, and 0.50–6.34 μg/m3, respectively. Formaldehyde, acetaldehyde and acetone levels after lacquering were 20.67–166.54, 0.07–23.24, and 9.13–54.90 μg/m3, respectively. Organic compound levels were found to be lower in indoor air after lacquering. The average MDA level in the urine of atopic dermatitis patients was reduced after lacquering compared to levels before lacquering as levels were recorded at 0.009±0.003 μmol/L and 0.014±0.007 μmol/L, respectively. The change of formaldehyde, acetaldehyde and benzaldehyde levels before and after lacquering was negatively related to the change in MDA level, but the correlation was not statistically significant (p>0.05).In this study, lacquering was shown to modify the indoor environment in the homes of atopic dermatitis patients by reducing formaldehyde, acetaldehyde, acetone, and benzaldehyde levels in indoor air and reducing urine MDA levels. These findings suggest that lacquer tree sap has the possibility to improve atopic dermatitis.

5-ALA induced fluorescent image analysis of actinic keratosis

In this study, we quantitatively analyzed 5-ALA induced fluorescent images of actinic keratosis using digital fluorescent color and hyperspectral imaging modalities. UV-A was utilized to induce fluorescent images and actinic keratosis (AK) lesions were demarcated from surrounding the normal region with different methods. Eight subjects with AK lesion were participated in this study. In the hyperspectral imaging modality, spectral analysis method was utilized for hyperspectral cube image and AK lesions were demarcated from the normal region. Before image acquisition, we designated biopsy position for histopathology of AK lesion and surrounding normal region. Erythema index (E.I.) values on both regions were calculated from the spectral cube data. Image analysis of subjects resulted in two different groups: the first group with the higher fluorescence signal and E.I. on AK lesion than the normal region; the second group with lower fluorescence signal and without big difference in E.I. between two regions. In fluorescent color image analysis of facial AK, E.I. images were calculated on both normal and AK lesions and compared with the results of hyperspectral imaging modality. The results might indicate that the different intensity of fluorescence and E.I. among the subjects with AK might be interpreted as different phases of morphological and metabolic changes of AK lesions.