Potential Role of Cytosolic RNA Sensor MDA5 as an Inhibitor for Keratinocyte Differentiation in the Pathogenesis of Psoriasis

Background@#Psoriasis is a chronic inflammatory skin disease. The etiology of psoriasis is not fully understood, but the genetic background is considered to be the most important factor. To date, many psoriasis-related genes have been discovered, but the role of many important genes has not been well understood. @*Objective@#The purpose of this study is to uncover possible roles of MDA5 in psoriasis. @*Methods@#Expression of MDA5 was investigated using immunohistochemistry. Then, MDA5 was overexpressed in keratinocytes using a recombinant adenovirus. @*Results@#As a result of immunohistochemical staining, the expression of MDA5 was significantly increased in the epidermis of psoriasis compared to normal skin. Similarly, the expression of MDA5 was increased in imiquimod-induced psoriasiform dermatitis model. In cultured keratinocytes, toll-like receptor 3 agonist poly(I:C) induced expression of MDA5 at both mRNA and protein levels. When MDA5 was overexpressed using a recombinant adenovirus, poly(I:C)-induced cytokine expression was significantly increased. Finally, MDA5 overexpression significantly inhibited calcium-induced differentiation of keratinocytes. @*Conclusion@#These results suggest that MDA5 increases in psoriasis and negatively regulates keratinocyte differentiation.

Potential Role of Cytosolic RNA Sensor MDA5 as an Inhibitor for Keratinocyte Differentiation in the Pathogenesis of Psoriasis

Background@#Psoriasis is a chronic inflammatory skin disease. The etiology of psoriasis is not fully understood, but the genetic background is considered to be the most important factor. To date, many psoriasis-related genes have been discovered, but the role of many important genes has not been well understood. @*Objective@#The purpose of this study is to uncover possible roles of MDA5 in psoriasis. @*Methods@#Expression of MDA5 was investigated using immunohistochemistry. Then, MDA5 was overexpressed in keratinocytes using a recombinant adenovirus. @*Results@#As a result of immunohistochemical staining, the expression of MDA5 was significantly increased in the epidermis of psoriasis compared to normal skin. Similarly, the expression of MDA5 was increased in imiquimod-induced psoriasiform dermatitis model. In cultured keratinocytes, toll-like receptor 3 agonist poly(I:C) induced expression of MDA5 at both mRNA and protein levels. When MDA5 was overexpressed using a recombinant adenovirus, poly(I:C)-induced cytokine expression was significantly increased. Finally, MDA5 overexpression significantly inhibited calcium-induced differentiation of keratinocytes. @*Conclusion@#These results suggest that MDA5 increases in psoriasis and negatively regulates keratinocyte differentiation.

Altered Mitochondrial Functions and Morphologies in Epithelial Cells Are Associated With Pathogenesis of Chronic Rhinosinusitis With Nasal Polyps

Purpose@#Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory disease of the nasal and paranasal sinus mucosa. The disease is associated with mitochondrial dysfunction, structural changes in the mitochondria, and reactive oxygen species (ROS) generation. This study investigated whether there are functional and morphological changes in the mitochondria in the epithelial cells of nasal polyps (NPs) and Staphylococcus aureus enterotoxin B (SEB)-stimulated nasal epithelial cells. @*Methods@#In all, 30 patients with CRSwNP and 15 healthy subjects were enrolled. Mitochondrial ROS (mtROS) and changes in mitochondrial functions and structures were investigated in the uncinate tissue (UT) of healthy controls, the UT or NPs of CRSwNP patients, and human nasal epithelial cells with or without SEB stimulation. @*Results@#Oxidative phosphorylation complexes showed various responses following SEB stimulation in the nasal epithelial cells, and their expressions were significantly higher in the NPs of patients with CRSwNP than in the UT of controls. Generation of mtROS was increased following SEB exposure in nasal epithelial cells and was reduced by pretreatment with MitoTEMPO, which is used as an mtROS scavenger. In the tissues, mtROS was significantly increased in the NPs of CRSwNP patients compared to the UT of controls or CRSwNP patients. The expressions of fusion- and fission-related molecules were also significantly higher in SEB-exposed nasal epithelial cells than in non-exposed cells. In tissues, the expression of fission (fission mediator protein 1)- and fusion (membrane and mitofusin-1, and optic atrophy protein 1)-related molecules was significantly higher in the NPs of CRSwNP patients than in UT of controls or CRSwNP patients. Transmission electron microscopy revealed elongated mitochondria in SEB-exposed nasal epithelial cells and epithelial cells of NPs. @*Conclusions@#Production of mtROS, disrupted mitochondrial function, and structural changes in nasal epithelial cells might be involved in the pathogenesis of CRSwNP.

Possible Role of Lysine Demethylase 2A in the Pathophysiology of Psoriasis

Background@#Psoriasis is a common chronic inflammatory skin disease. The development of psoriasis is dependent on many intercellular events such as innate immunity and T cell-mediated inflammation. Furthermore, genetic factors are strongly implicated in the pathophysiology of psoriasis. Although a variety of susceptible genes are identified, it is likely that many important genes remain undisclosed. @*Objective@#The aim of this study is to investigate the possible role of lysine demethylase 2A (KDM2A) in the pathophysiology of psoriasis. @*Methods@#We examined the expression of KDM2A using a well established imiquimod-induced psoriasiform dermatitis model. @*Results@#Immunohistochemistry analysis showed that expression of KDM2A was increased in imiquimod-induced psoriasiform dermatitis. Consistent with this result, KDM2A level was markedly increased in the epidermis of psoriatic patient. When keratinocytes were stimulated with TLR3 agonist poly(I:C), KDM2A was increased at both the mRNA and protein levels. Poly(I:C) increased the expression of psoriasis-related cytokines including tumor necrosis factor-α, interleukin-8, and CCL20, and KDM2A inhibitor daminozide enhanced the poly(I:C)-induced cytokine expression. Finally, topical co-application of imiquimod and daminozide exacerbated the imiquimod-induced psoriasiform dermatitis. @*Conclusion@#Together, these results suggest that KDM2A is increased to negatively regulate the inflammatory reaction of epidermal keratinocytes in psoriasis.

Altered Mitochondrial Functions and Morphologies in Epithelial Cells Are Associated With Pathogenesis of Chronic Rhinosinusitis With Nasal Polyps

Purpose@#Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory disease of the nasal and paranasal sinus mucosa. The disease is associated with mitochondrial dysfunction, structural changes in the mitochondria, and reactive oxygen species (ROS) generation. This study investigated whether there are functional and morphological changes in the mitochondria in the epithelial cells of nasal polyps (NPs) and Staphylococcus aureus enterotoxin B (SEB)-stimulated nasal epithelial cells. @*Methods@#In all, 30 patients with CRSwNP and 15 healthy subjects were enrolled. Mitochondrial ROS (mtROS) and changes in mitochondrial functions and structures were investigated in the uncinate tissue (UT) of healthy controls, the UT or NPs of CRSwNP patients, and human nasal epithelial cells with or without SEB stimulation. @*Results@#Oxidative phosphorylation complexes showed various responses following SEB stimulation in the nasal epithelial cells, and their expressions were significantly higher in the NPs of patients with CRSwNP than in the UT of controls. Generation of mtROS was increased following SEB exposure in nasal epithelial cells and was reduced by pretreatment with MitoTEMPO, which is used as an mtROS scavenger. In the tissues, mtROS was significantly increased in the NPs of CRSwNP patients compared to the UT of controls or CRSwNP patients. The expressions of fusion- and fission-related molecules were also significantly higher in SEB-exposed nasal epithelial cells than in non-exposed cells. In tissues, the expression of fission (fission mediator protein 1)- and fusion (membrane and mitofusin-1, and optic atrophy protein 1)-related molecules was significantly higher in the NPs of CRSwNP patients than in UT of controls or CRSwNP patients. Transmission electron microscopy revealed elongated mitochondria in SEB-exposed nasal epithelial cells and epithelial cells of NPs. @*Conclusions@#Production of mtROS, disrupted mitochondrial function, and structural changes in nasal epithelial cells might be involved in the pathogenesis of CRSwNP.

Erratum: Possible Role of Single Stranded DNA Binding Protein 3 on Skin Hydration by Regulating Epidermal Differentiation

The authors would like to change the corresponding author of the article.

Possible Role of Single Stranded DNA Binding Protein 3 on Skin Hydration by Regulating Epidermal Differentiation

BACKGROUND: Skin hydration is a common problem both in elderly and young people as dry skin may cause irritation, dermatological disorders, and wrinkles. While both genetic and environmental factors seem to influence skin hydration, thorough genetic studies on skin hydration have not yet been conducted. OBJECTIVE: We used a genome-wide association study (GWAS) to explore the genetic elements underlying skin hydration by regulating epidermal differentiation and skin barrier function. METHODS: A GWAS was conducted to investigate the genetic factors influencing skin hydration in 100 Korean females along with molecular studies of genes in human epidermal keratinocytes for functional study in vitro. RESULTS: Among several single nucleotide polymorphisms identified in GWAS, we focused on Single Stranded DNA Binding Protein 3 (SSBP3) which is associated with DNA replication and DNA damage repair. To better understand the role of SSBP3 in skin cells, we introduced a calcium-induced differentiation keratinocyte culture system model and found that SSBP3 was upregulated in keratinocytes in a differentiation dependent manner. When SSBP3 was overexpressed using a recombinant adenovirus, the expression of differentiation-related genes such as loricrin and involucrin was markedly increased. CONCLUSION: Taken together, our results suggest that genetic variants in the intronic region of SSBP3 could be determinants in skin hydration of Korean females. SSBP3 represents a new candidate gene to evaluate the molecular basis of the hydration ability in individuals.

Immunohistochemical Study of Psoriasis-related Gene Expression in Imiquimod-induced Psoriasis-like Mouse Model / 대한피부과학회지

BACKGROUND: Psoriasis is a chronic inflammatory skin disease with an incidence of 0.5~3% of the worldwide population. The pathogenesis of psoriasis is related to dysregulated keratinocyte function and immune reactions. Notably, genetic factors are considered important etiological contributors. Globally, several researchers have recently performed genome-wide association studies (GWAS) to identify the genes related with psoriasis. OBJECTIVE: We aimed to investigate the expression pattern of 2 candidate genes that were identified by GWAS. These include interleukin 28 receptor alpha (IL28RA) and CUB and Sushi multiple domains 1 (CSMD1). METHODS: We applied imiquimod cream to develop a psoriasis-like mouse model and obtained skin tissue. We performed immunohistochemistry to detect the expression of IL-28A and CSMD1. RESULTS: IL28RA expression increased at an early time point such as 1 day after the topical application of 5% imiquimod cream. However, its expression returned to baseline levels 2 weeks after the topical application of imiquimod cream. CSMD1 expression also increased after the topical application of imiquimod, with increased expression particularly observed in the upper epidermal layer. Notably, CSMD1 expression decreased 7 days after imiquimod cream application. CONCLUSION: These results suggest that IL28RA and CSMD1 may play key roles in the pathogenesis of psoriasis.

Retraction: Ampelopsis japonica Makino Extract Inhibits the Inflammatory Reaction Induced by Pathogen-Associated Molecular Patterns in Epidermal Keratinocytes

This article has been retracted following a review by the Editorial Board.

Ampelopsis japonica Makino Extract Inhibits the Inflammatory Reaction Induced by Pathogen-Associated Molecular Patterns in Epidermal Keratinocytes

BACKGROUND: Keratinocytes are the major cells in epidermis, providing barrier components such as cornified cells through the sophisticated differentiation process. In addition, keratinocytes exerts their role as the defense cells via activation of innate immunity. It has been known that pathogen-associated molecular patterns (PAMPs) including double-strand RNA and nucleotides can provoke inflammatory reaction in keratinocytes. OBJECTIVE: The aim of this study is to evaluate the effect of Ampelopsis japonica Makino extract (AE) on PAMPs-induced inflammatory reaction of keratinocytes. METHODS: The effects of AE were determined using poly (I:C)-induced inflammation and imiquimod-induced psoriasiform dermatitis models. RESULTS: In cultured keratinocytes, AE significantly inhibited poly(I:C)-induced expression of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor-α. AE significantly inhibited poly(I:C)-induced release of caspase-1 active form (p20), and down-regulated nuclear factor-κB signaling pathway. In imiquimod-induced psoriasiform dermatitis model, topical application of AE resulted in significant reduction of epidermal hyperplasia. CONCLUSION: These results suggest that AE may be a potential candidate for the treatment of skin inflammation.

Study of a "wing-type" implant on stress distribution and bone resorption at the alveolar crest

OBJECTIVES: Implants connect the internal body to its external structure, and is mainly supported by alveolar bone. Stable osseointegration is therefore required when implants are inserted into bone to retain structural integrity. In this paper, we present an implant with a "wing" design on its area. This type of implant improved stress distribution patterns and promoted changes in bone remodeling. MATERIALS AND METHODS: Finite element analysis was performed on two types of implants. One implant was designed to have wings on its cervical area, and the other was a general root form type. On each implant, tensile and compressive forces (30 N/m2, 35 N/m2, 40 N/m2, and 45 N/m2) were loaded in the vertical direction. Stress distribution and displacement were subsequently measured. RESULTS: The maximum stresses measured for the compressive forces of the wing-type implant were 21.5979 N/m2, 25.1974 N/m2, 29.7971 N/m2, and 32.3967 N/m2 when 30 N/m2, 35 N/m2, 40 N/m2, and 45 N/m2 were loaded, respectively. The maximum stresses measured for the root form type were 23.0442 N/m2, 26.9950 N/m2, 30.7257 N/m2, and 34.5584 N/m2 when 30 N/m2, 35 N/m2, 40 N/m2, and 45 N/m2 were loaded, respectively. Thus, the maximum stresses measured for the tensile force of the root form implant were significantly higher (about three times greater) than the wing-type implant. The displacement of each implant showed no significant difference. Modifying the design of cervical implants improves the strength of bone structure surrounding these implants. In this study, we used the wing-type cervical design to reduce both compressive and tensile distribution forces loaded onto the surrounding structures. In future studies, we will optimize implant length and placement to improve results. CONCLUSION: 1. Changing the cervical design of implants improves stress distribution to the surrounding bone. 2. The wing-type implant yielded better results, in terms of stress distribution, than the former root-type implant.

Tinea Incognito Caused by Application of 0.03% Tacrolimus (Protopic(R)) Ointment in Atopic Dermatitis Patient / 대한의진균학회지

We report a case of tinea incognito in a 29-year-old man after applying the 0.03% tacrolimus ointment. He was known atopic dermatitis patient and has been treated with intermittent application of tacrolimus. For his facial pruritus 0.03% tacrolimus ointment was prescribed, and after one week he developed annularly grouped erythematous plaques and patches around the ointment-applied area. The KOH smear revealed multiple fungal hyphae. Dermatologists should be aware of the possibility of topical tacrolimus to be the causative agent for tinea incognito.

Recalcitrant Atopic Dermatitis Treated with Omalizumab

Atopic dermatitis (AD) is a chronic cutaneous inflammatory disease. Various categories of therapeutic medications are used for treating AD. Omalizumab is a monoclonal anti-IgE antibody that binds to IgE molecules at the high-affinity receptor (FcepsilonRI) binding site. Therefore, omalizumab can be used as a potential new systemic treatment agent for recalcitrant AD patients with elevated IgE levels. A 34-year-old man had been treated for AD with several topical and oral agents. However, he was refractory to these therapies and his serum IgE levels were very high. We treated him with omalizumab. After 8 months of the treatment, his symptoms were notably improved and the SCORAD index was decreased. Thus, we report on the first case of recalcitrant AD that was successfully treated with omalizumab in Korea.

Behcet disease with superior vena cava thrombus in a patient presenting delayed facial wound healing: A case report

The Long Term Efficacy and Relapse Rate of Itraconazole Pulse Therapy Versus Terbinafine Continuous Therapy for Toenail Onychomycosis: a 96-week follow-up study / 대한의진균학회지

No abstract available.