Weon Ju Lee

Influence of substance-P on cultured sebocytes.

Acne is a complex, chronic and common skin disorder of pilosebaceous units. Although it is known that exacerbation of acne results from emotional stress, the nature of the association between stress and acne remains unclear. This is due in part to the lack of substantial evidence regarding the participation of cutaneous neurogenic factors in the pathogenesis of acne. Culture of sebocytes provides a new insight into the participation of neuropeptides, notably substance P (SP), in the pathophysiology of acne. To examine the possible involvement of neurogenic factors in the pathogenesis of acne, we used immunohistochemistry and RT-PCR to compare the expression of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), peroxisome proliferators activated receptors-γ (PPAR-γ) on the cultured sebocytes stimulated by SP. IL-1 is primarily proinflammatory cytokines to stimulate the expression of genes associated with inflammation. IL-6 is a pleiotropic cytokine with a wide range of biological activities and regulates inflammation. TNF-α is a pleiotropic pro-inflammatory cytokine that exerts multiple biologic effects. PPAR-γ is a nuclear hormone receptor and plays a unique role in stimulating sebocyte lipogenesis. More numerous immunoreactivity to IL-1, IL-6, TNF-α and PPAR-γ and increased RNA amplification for IL-1, IL-6, TNF-α and PPAR-γ were observed after addition of SP compared with the control. This study reveals that SP is involved in the pathogenesis of acne.

Topical ALA-Photodynamic Therapy for Acne Can Induce Apoptosis of Sebocytes and Down-regulate Their TLR-2 and TLR-4 Expression

BACKGROUND Although photodynamic therapy (PDT) is widely performed for acne, little is known about its exact therapeutic mechanism. OBJECTIVE We aimed to estimate the efficacy and safety of PDT on acne and to discover its mode of action. METHODS We performed PDT on 12 patients with mild to moderate acne. The clinical efficacy was assessed by counting the acne lesions and measuring the sebum secretion before and after PDT. In addition, we took biopsy samples from the peri-lesional areas before and after 3-session of PDT. To examine the degree of apoptosis of the sebaceous follicles, TUNEL assay was performed. To investigate the changes of toll-like receptor (TLR)-2 and TLR-4 expression after PDT, immunohistochemical stainings were also carried out. Finally, we performed TUNEL assay using the cultured sebocytes to confirm the apoptosis of sebocytes in vitro after PDT. RESULTS There was a significant reduction in the number of inflammatory acne lesions after PDT, compared to baseline (p<0.05). Sebum excretion significantly decreased 2 weeks after the first PDT session except for one patient (p<0.05). The TUNEL positive cells in the peri-lesional sebaceous glands after PDT markedly increased, compared with those of before PDT. A decrease in TLR-2 and TLR-4 expression by sebaceous glands and epidermis after PDT was 50% and 30%, respectively. CONCLUSION Our results demonstrate that apoptosis of the sebaceous glands is associated with improvement of acne by PDT. PDT has shown to down-regulate TLR-2 and TLR-4 expression in the sebaceous glands and epidermis of acne patients.

A multicenter study on extramammary Paget's disease in Korea.

Background  There has been little research on extramammary Paget’s disease (EMPD) conducted in Asia.

Effect of dihydrotestosterone on the upregulation of inflammatory cytokines in cultured sebocytes

Acne is a complex, chronic and common skin disorder of pilosebaceous units. Hyperkeratinization of keratinocytes, increased sebum excretion from sebocytes via androgen stimulation and inflammatory cytokines are the major factors involved in the pathophysiology of acne. In addition, it is known that keratinocytes play an important role in acne synthesizing a number of inflammatory cytokines. However, the nature of the association between inflammatory cytokines and sebocytes in acne remains unclear. Culture of sebocytes provides a new insight into the participation of dihydrotestosterone (DHT) in the production of inflammatory cytokines in acne. To examine the possible involvement of DHT in the production of inflammatory cytokines in the cultured sebocytes, we used immunohistochemistry and RT-PCR to compare the expression of interleukin-1 (IL-1), IL-6, tumor necrosis factor-α (TNF-α). Upregulation of IL-6 and TNF-α in immunohistochemistry, and increase in RNA amplification for IL-6 and TNF-α were observed after addition of DHT compared with the control. This study suggests that DHT may not only be involved in sebum production but also in production of proinflammatory cytokines in acne.

Decreasing Prevalence of Microsporum canis Infection in Korea: Through Analysis of 944 Cases (1993–2009) and Review of Our Previous Data (1975–1992)

Since 1957, Microsporum (M.) canis has been one of the common causative agents of dermatophytosis in Korea. We analyzed 944 patients infected with M. canis who attended outpatient clinic over a 17-year period (1993–2009). M. canis infections were diagnosed by mycological examinations, including direct microscopic examinations with 15% KOH and cultures on potato dextrose agar complemented with 0.5% chloramphenicol. Mycological examinations confirmed 164,903 cases of dermatophytosis, 944 (0.6%) of which were M. canis infections. The annual prevalence of patients with M. canis infection was the highest in 2002 (91 cases). Then, the prevalence of patients with M. canis infection markedly decreased until 2008 (15 cases). The ratio of male to female patients was 0.65:1, but the ratio in children under the age of 15 was 1.14:1 and was 0.20:1 in adults. Seasonally, 274 cases occurred in winter, showing higher incidence than in other seasons. There was a difference in the clinical forms of M. canis infections between children and adults; tinea (T.) capitis was the most common form in children, but T. corporis was the most common in adults. We demonstrate that the decreasing prevalence of M. canis infections over the study period has been noted in Korea.

Parry-Romberg Syndrome with En Coup de Sabre

Parry-Romberg syndrome (PRS) is a relatively rare degenerative disorder that is poorly understood. PRS is characterized by slowly progressing atrophy affecting one side of the face, and is frequently associated with localized scleroderma, especially linear scleroderma, which is known as en coup de sabre. This is a report of the authors experiences with PRS accompanying en coup de sabre, and a review of the ongoing considerable debate associated with these two entities. Case 1 was a 37-year-old woman who had right hemifacial atrophy with unilateral en coup de sabre for seven years. Fat grafting to her atrophic lip had been conducted, and steroid injection had been performed on the indurated plaque of the forehead. Case 2 was a 29-year-old woman who had suffered from right hemifacial atrophy and bilateral en coup de sabre for 18 years. Surgical corrections such as scapular osteocutaneous flap and mandible/maxilla distraction showed unsatisfying results.

Disruption of barrier function in dermatophytosis and pityriasis versicolor

Dermatophytes have the ability to form molecular attachments to keratin and use it as a source of nutrients, colonizing keratinized tissues, including the stratum corneum of the skin. Malassezia species also affect the stratum corneum of the skin. Therefore, dermatophytosis and pityriasis versicolor of the skin are thought to be important factors of profound changes in skin barrier structure and function. We aimed to describe the changes in transepidermal water loss (TEWL), stratum corneum hydration, and skin pH in the lesions of the dermatophytosis and pityriasis versicolor. Thirty‐six patients with dermatophytosis (14 with tinea cruris, 13 with tinea corporis and nine with tinea pedis or tinea manus) and 11 patients with pityriasis versicolor were included in this study. TEWL, stratum corneum conductance and skin pH were determined by biophysical methods to examine whether our patients exhibited changes in barrier function. Dermatophytosis and pityriasis versicolor except tinea pedis and tinea manus showed highly significant increase in TEWL compared with adjacent infection‐free skin. Hydration was significantly reduced in lesional skin compared with adjacent infection‐free skin. From this study, infections with dermatophytes and Malassezia species on the body can alter biophysical properties of the skin, especially the function of stratum corneum as a barrier to water loss. On the contrary, infections with dermatophytes on the palms and soles little affect the barrier function of the skin.

Expression of inflammatory biomarkers from cultured sebocytes was influenced by treatment with vitamin D

Background: Inflammatory cytokines are the key factor in the pathophysiology of acne. It is well known that keratinocytes synthesize many kinds of inflammatory cytokines. In addition, it is reported that inflammatory cytokines are also expressed from sebocytes, which originate from the same stem cells with keratinocytes. Aim: To clarify changes in the expression of inflammatory biomarkers from cultured sebocytes after treatment with vitamin D. Materials and Methods: Reverse transcription-polymerase chain reaction (RT-PCR) was done to measure changes in the expression of inflammatory biomarkers, including interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor-α (TNF-α), and several subtypes of matrix metalloproteinases (MMPs) after treatment of a group of cultured sebocytes with vitamin D. Vitamin D receptor (VDR) small interfering RNA (siRNA) was added in the other group of cultured sebocytes to assure the role of vitamin D on the expression of inflammatory biomarkers. Enzyme-linked immunosorbent assay (ELISA) was also performed in the vitamin D-treated sebocytes. Results: Cultured sebocytes showed non-significant changes in the gene expression of inflammatory biomarkers after treatment with vitamin D. In cultured sebocytes treated with a VDR siRNA, the expression of inflammatory biomarkers was not blocked after treatment with vitamin D. ELISA showed a significant decrease in the expression of IL-6, IL-8, and MMP-9, but a significant increase in the expression of MMP-1 and MMP-3, after treatment with vitamin D (10-6 M). Conclusion: Expression of inflammatory biomarkers is influenced by treatment with vitamin D in cultured sebocytes, but not through VDR.

Potential Immunoinflammatory Role of Staphylococcal Enterotoxin A in Atopic Dermatitis: Immunohistopathological Analysis and in vitro Assay

Background The underlying mechanism of atopic dermatitis (AD) exacerbated by Staphylococcus aureus has not been established. However, we demonstrated recently that the majority of S. aureus strains colonized in the skin of Korean AD patients carried genes encoding staphylococcal enterotoxin A (SEA) and/or toxic shock syndrome toxin-1 (TSST-1). Objective To clarify the role of staphylococcal superantigen, SEA in AD. Methods With the lesional skin of 9 AD patients and normal looking skin of one healthy adult, we examined first the expression of SEA, staphylococcal enterotoxin B (SEB), and TSST-1 using immunohistochemical analysis. In addition, we investigated the effects of SEA on the expression of inflammation-related adhesion molecules and cytokines in human HaCaT keratinocytes and Human Umbilical Vein Endothelial Cells (HUVECs) by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and enzyme-linked immunosorbent assay. Results Staphylococcal protein A (SPA) and SEA were detected with increased immunoreactivity in AD patients. However, TSST-1 showed mild-to-moderate immunoreactivity in AD patients, whereas SEB was minimally detected. In the double immunofluorescence investigation, SEA and SPA were well co-localized. SEA induced upregulation of adhesion molecules and elicited inflammatory responses in HaCaT keratinocytes and HUVECs. Conclusion This study demonstrates the importance of SEA as an immunoinflammatory triggering factor of AD in Koreans.

Repeated Paradoxical Aggravation of Preexisting Psoriasis during Infliximab Treatment for Crohn's Disease

As more rheumatologists and dermatologists have begun to use biological agents such as TNF-alpha blocker, they have confronted an unexpected complication: psoriasis was paradoxically aggravated or induced by the TNF-alpha blocker. Although it is not a common complication of TNF-alpha blocker, this aggravation may be more common than previously thought. To our knowledge, most reports about TNF-alpha blocker-induced psoriasis have been limited to western countries while only a few cases have been reported in Korea and Japan. In addition, new onset of pustular psoriasis by TNF-alpha blocker has been reported more commonly than worsening of preexisting psoriasis. Now we report a patient whose preexisting psoriasis vulgaris was aggravated repeatedly after using the TNF-alpha blocker, infliximab, to control Crohns disease, which is a rare rheumatologic disease in Korea.