Effect of Transcription Factor Decoy for NF-κB on the TNF-α Induced Cytokine and ICAM-1 Expression in Cultured HaCaT cells

BACKGROUND: Psoriasis is the most prevalent T-cell-mediated inflammatory skin disease in humans. Numerous cytokines and adhesion molecules are expressed in the skin lesion of psoriasis such as TNF-α, IL-1, IL-6, VCAM-1 and ICAM-1. All of them contain at least one binding site for the transcription factor NF-κB. TNF-α activates NF-κB and many other transcription factors. Thus, transcription and expression of many genes involved in the inflammatory process may be influenced by TNF-α. OBJECTIVE: The purpose of this study was to study the effect of synthetic double-stranded DNA with high affinity for the NF-κB binding site on the TNF-α induced proinflammatory cytokines and ICAM-1 gene expression in the HaCaT cells. MATERIAL AND METHODS: We examined whether inhibition of NF-κB activity by oligodeoxynucleotides (ODN) decoy for NF-κB blocks TNF-α induced cytokines such as IL-la, IL-1 a, IL-6 and ICAM-1 expression with electrophoretic mobility shift assay (EMSA) and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: In EMSA, TNF-α treatment (10 ng/ml) induced the activation of NF-κB. The NF-κB binding activity in the TNF-α treated HaCaT cells increased 5.0-fold compared to non-treated group. Next, we examined the effect of liposome mediated NF-κB decoy oligonucleotides (ODN) transfection. After transfection of the NF-κB decoy ODN, TNF-α increased NF-κB binding activity to 1.9-fold of non-treated group. Accordingly the transfection of NF-κB decoy ODN inhibited the TNF-α induced NF-κB binding activity up to 63%. RT-PCR analysis revealed that the transfection of NF-κB decoy ODN inhibited TNF-α induced cytokines and ICAM-1 mRNA expression. CONCLUSION: Taken together, our results suggest the potential utility of NF-κB decoy technique for biologic therapy of psoriasis.

Skin Lesions Developing in Renal Transplantation Recipients / 대한피부과학회지

BACKGROUND: As the renal transplantation is rapidly becoming a standard treatment of end stage renal disease, a varieties of skin lesions in renal transplant recipients are being encountered in Korea. However, there have been little studies concerning the incidence and clinical feature of skin lesions has not been well addressed yet. OBJECTIVE: We examined the skin manifestations in renal transplant recipients. METHOD: We attempted to assess the dermatologic problems in 58 renal transplant recipients, who had been managed at Keimyung University Medical center between December, 2001, and July, 2002. RESULTS: The results are summarized as follows; Among the 58 patients, the number of male and female patients were 31(53.4%) and 27(46.6%) respectively. The mean age was 38.3 years and the mean duration of renal transplatant was 38.7 months. They had one more skin lesions. Among the 58 patients, skin infection was found in 61(105%), drug-associated skin lesions in 31(53.4%), malignant skin tumor in 0(0%) and other skin lesions in 6(10.3%). Viral infections were VZV infection(15 cases, 25.9%), HPV infection(11 cases, 19%), HSV infection(7 cases, 12.1%) and molloscum contagiosum(2 cases, 3.4%). Fungal infections were superficial mycosis(16cases, 27.6%) and deep mycosis(1 case, 1.7%). Bacterial infection was found in 5(8.6%). Drug-associated skin lesions were hypertrichosis(17 cases, 29.3%), acne(11 cases, 19%), xerosis(7 cases, 12.1%), facial flusing, purpura and gingival hyperplasia(3 cases, 5.2%), respectively, telangiectasis and urticaria(2cases, 3.4%) respectively and alopecia(1 case, 1.7%). Other skin lesions included seborrheic dermatitis(8 cases, 13.8%), nummular dermatitis(3 cases, 5.2%), prurigo nodularis, scleredema, seborrheic keratosis and toxic erythema(1 case, 1.7%). CONCLUSION: Long term use of immunosuppresive agents is associated with high incidences of skin disease. Education of patients and medical staff for early detection and treatment of skin lesions is important.

A Case of Zosteriform Cutaneous Metastasis / 대한피부과학회지

We report a case of zosteriform cutaneous metastasis from breast cancer in a 62-year-old female patient who had painful confluent hard papules over left side of chest. Histopathologic examinations of the cutaneous lesion revealed neoplastic cell, which showing glandular structure and multifocal tumor emboli within dilated lymphatics, infiltrating in the dermis. She was treated with radiotherapy and chemotherapy.

The Examination of PUVA-Induced Dermatologic and Ophthalmologic Manifestations in Systemic PUVA Therapy / 대한피부과학회지

BACKGROUND: Systemic PUVA therapy is a widely used method for treatment of vitiligo and psoriasis. However, there have been few studies concerning complications of systemic PUVA therapy. OBJECTIVE: We examined the dermatologic and ophthalmologic manifestations in patients receiving PUVA therapy. METHOD: We studied 42 patients who received systemic PUVA therapy for more than six months in our department. RESULTS: The results are summarized as follows. 1. Among the 42 patients, the number of male and female patients were 18(42.9%) and 24(57.1%) respectively. The mean age at the start of PUVA was 42 years and mean cumulative UVA dase was 996 J/cm2. 2. Among the 42 patients, hyperpigmentation found in 9(21.4%), PUVA lentigo in 8(19.0%), pruritus in 5(11.9%) and burn in 3(7.1%). 3. The ophthalmologic manifestations were conjunctivitis(13 cases, 31.0%), pteygium(7 cases, 16.7%), pingueculum(6 cases, 14.3%) and cataract(3 cases, 7.1%). CONCLUSION: Long term exposure to PUVA causes chronic clinical side effects of PUVA. Therefore careful follow-up of patients who receive long term PUVA therapy is necessary.

Nicotine Down-regulates COL1A2 Promoter in Cultured Human Skin Fibroblasts

BACKGROUND: It has become generally accepted that cigarette smoking contributes to accelerated coronary and peripheral vascular disease, pulmonary fibrosis and periodontal disease. Moreover, it has been postulated that cigarette smoking causes skin-aging. Many of cutaneous manifestations of nicotine which is a major component of the particulate phase of tobacco smoke are related to its vasoconstrictive and thrombotic effects on the peripheral vascular system. How-ever, direct effect of nicotine on extracellular matrix (ECM) proteins including collagens is not well established. OBJECTIVE: To evaluate the effect of nicotine on type I collagen gene expression in cultured human skin fibroblasts. METHODS: After exposure to different doses of nicotine on cultured human skin fibroblasts, we examined the expressions of α1(I) procollagen gene and fibronectin gene by Northern blot analysis and chloramphenicol acetyltransferase (CAT) assay with CAT construct containing the 3.5 kb COL1A2 promoter. RESULTS: In Northern blot hybridization, steady-state levels of α1(I) procollagen mRNA were decreased 0.8-fold at 1 µg/mL of nicotine, 0.5-fold at 10 µg/mL and 0.2-fold at 100 µg/mL, compared to untreated control. Those of fibronectin mRNA were decreased 0.9-fold, 0.7-fold, and 0.3-fold, respectively. In CAT assay, the relative COL1A2 CAT activity was 1.0 in the untreated control, 0.7 at a concentration of 1 µg/mL of nicotine, 0.5 at 10 µg/mL, and 0.3 at 100 µg/mL. CONCLUSION: These results indicate that nicotine is a down-regulator of collagen gene expression at transcriptional level in vitro. We speculate that nicotine may contribute to the skin-aging by modulation of extracellular matrix gene expression including collagen as well as by its vasoconstrictive and thrombotic effects.

A Case of Perforating Calcific Elastosis in a Multiparous Women after Laparoscopic Surgery / 대한피부과학회지

Perforating calcific elastosis is a localized cutaneous acquired disorder most frequently in obese, multiparous, middle-aged women. We report a case of perforating calcific elastosis in a 66-year-old multiparous woman who had asymptomatic yellowish cobblestoned plaque with keratotic papules scattered on its surface in the periumbilical region. She have been treated to laparoscopic surgery 5 years ago. The biopsy specimen showed basophilic calcified elastic fibers in the dermis that undergo transepidermal elimination. The von Kossa stain showed dense deposition of calcium in this area.

A Case of Cutaneous Metastasis from Carcinoma of the Hypopharynx / 대한피부과학회지

Distant metastases from squamous cell carcinoma of the head and neck occur at many sites, most commonly lung and bone. Metastases to the skin are unusual, and account for fewer than 10% of all distant metastatic lesions. A 61-year-old man developed cutaneous metastasis two years later after the diagnosis of squamous cell carcinoma of the hypopharynx had been made. He was presented with asymptomatic multiple erythematous hard nodules with telangiectasia on the right shoulder. This lesion was diagnosed histologically as poorly differentiated squamous cell carcinoma. The skin metastases improved with radiotherapy and palliative chemotherapy, including cisplantin, 5-fluorouracil.

A Case of Subcutaneous Panniculitic T-cell Lymphoma / 대한피부과학회지

Subcutaneous panniculitic T-cell lymphoma(SPTCL) is a rare subtype of peripheral T-cell lymphoma that clinically and histologically mimics benign panniculitis. It represents subcutaneous nodules predominatly on extremities and trunk and hemophagocytic syndrome almost leading to death. A 29-year-old women presented with multiple tender subcutaneous nodules on lower abdomen and extremities for 6 months often with fevers and chills. There was no hepatosplenomegaly or lymphadenopathy. Skin biopsy specimen showed dense diffuse infiltration of atypical lymphocytes in the subcutis, with extensive fat necrosis and karyorrhexis. The immunophenotypic studies showed a cytoxic T-lymphocyte profile, i.e., LCA+, UCHL+, CD8+, CD20-, CD30-, and CD56-. In immunohistochemical studies for the Ebstein-Barr virus resulted in a negative finding. On the basis of the clinical and histological finding, we established the diagnosis of SPTCL.

Three Cases of Recessive Dystrophic Epidermolysis Bullosa-mitis / 대한피부과학회지

Recessive dystrophica epidermolysis bullosa(RDEB) is rare, chronic non - inflammatory bullous disease of hereditary trait, which produces blister formation in early childhood. A localized, less severe form, often called RDEB-mitis, occurs at birth and usually involves the acral areas, with atrophic scarring of the joint surfaces and nail dystrophy but little mucosal involvement. Severe RDEB is a multilating disease, known also as the Hallopeau-Siemens (HS) varient. We report three cases which developed at birth and infancy, respectively. Bullae, atrophic scars were noted on the knees and ankles, and milia on the both hands and feet. Histologically, sections from the old blister lesion showed characteristic separation of the epidermis from the dermis forming bulla. Identification of the mutations COL7A1 gene was revealed by direct sequencing of each exon. We present three cases of RDEB-mitis considering the abscence of family history with clinical, histological and molecular analysis findings.

The Effect of Nicotine on Elastin Gene Expression in Cultured Skin Fibroblasts / 대한피부과학회지

BACKGROUND: The elastic fibers are a major fibrillar component of the extracellular matrix of several organs, and their presence provides elastic properties to these tissues. A variety of cytokines, growth factors, and hormones have been shown to modulate elastin gene expression. So far most interest increased the effects of external environment on elastin metabolism in the skin. It has become generally accepted that cigarette smoking contributes to accelerated coronary and peripheral vascular disease, pulmonary fibrosis and periodontal disease. Nicotine is a major component of the particulate phase of tobacco smoke. OBJECTIVE: Only little is known about the molecular and cellular mechanism underlying the effect of nicotine on the skin fibroblasts. Our study was performed to determine the effects of nicotine on elastin gene expression. METHOD: In this study, the effects of nicotine were examined by Northern blot hybridization, chloramphenicol acetyltransferase (CAT) assay, and laser scanning microscopy in cultured human fibroblasts. RESULTS: In Northern blot hybridization, steady-state levels of elastin mRNA were decreased 0.9-fold at 1 microgram/mL of nicotine, 0.7-fold at 10 microgram/mL and 0.5-fold at 100 microgram/mL, compared to untreated control. Nicotine caused a marked alteration in the elastin mRNA expression in a dose-related fashion. In CAT assay, the relative elastin CAT activity was 1.0 in the untreated control, 0.9 at a concenturation of 1 microgram/mL, 0.3 at 10 microgram/mL, and 0.2 at 100 microgram/mL. Nicotine caused a marked decrease on elastin promoter activity. In laser scanning microscopy, the immunosignal for elastin in nicotine-treated fibroblasts shows in less intense than in untreated control. CONCLUSION: These results indicate that nicotine may be a powerful down-regulator of elastin production, suggesting transcriptional depression of gene expression in cultured skin fibroblasts.

A Case of Familial Benign Chronic Pemphigus Treated With Carbon Dioxide Laser Vaporization / 대한피부과학회지

Familial benign pemphigus is a skin disease with recurrent blistering lesions, mainly in the neck and intertriginous areas. The course of the disease is characterized by spontaneous exacerbations and remissions. The many remedies for this disorder include topical and systemic glucocorticosteroids, and antibacterial and antimycotic agents. However, these therapies usually do not prolong the remission periods. Surgical treatments, such as skin graft, have been more successful. Laser treatment has reported to be effective in recurrent familial benign chronic phemphigus. Here we report a case of familial benign chronic phemphigus that was treated with carbin dioxide laser.

A Case of Familial Benign Chronic Pemphigus Treated With Carbon Dioxide Laser Vaporization / 대한피부과학회지

Familial benign pemphigus is a skin disease with recurrent blistering lesions, mainly in the neck and intertriginous areas. The course of the disease is characterized by spontaneous exacerbations and remissions. The many remedies for this disorder include topical and systemic glucocorticosteroids, and antibacterial and antimycotic agents. However, these therapies usually do not prolong the remission periods. Surgical treatments, such as skin graft, have been more successful. Laser treatment has reported to be effective in recurrent familial benign chronic phemphigus. Here we report a case of familial benign chronic phemphigus that was treated with carbin dioxide laser.

Two Cases of Cutaneous Metastasis from Carcinoma of Cervix / 대한피부과학회지

Metastasis to the skin from internal malignant neoplasms are an uncommon and often preterminal event. Although carcinoma of the cervix is the fourth most common malignancy in women, cutaneous involvement originating from cervical cancer is particularly unusual, even in the terminal stages of disease. We report two cases of cutaneous metastasis from cervical cancer. Case one was a 57-year-old woman, who has been treated with radiotherapy and chemotherapy for an cervical cancer(Stage IIa) since 11 years ago. She showed multiple grouped shallow ulcerative nodules and papules on the external genitalia 1 month ago. Another case was a 46-year-old woman noted irregular vaginal bleeding, and pelvic examination revealed an cervical cancer(Stage IIb) for 2 years ago. She visited our clinic because of swelling of the right leg and multiple erythematous nodules and ulcerative lesion on the right thigh for 2months. Histopathologic findings showed skin tumors, which were considered to originate from the cervix.

A Case of Classic Kaposi's Sarcoma Showing Good Response to Radiotherapy / 대한피부과학회지

Kaposi's sarcoma is a neoplasm of multifocal origin which manifests primarily as vascular nodules in the skin and other organs. We report a case of classic Kaposi's sarcoma in a 79-year-old man who had asymptomatic dark-brown macules, papules and nodules on his Rt. lower extremities. The biopsy specimen showed typical histopathologic features of Kaposi's sarcoma including dilated, bizarre-shaped vessels, endothelial cell proliferation, and spindle cell formation with vascular slits throughout the dermis. Many of the spindle-shaped cells associated with the proliferating vessels in Kaposi's sarcoma lesion expressed factor VIII-related antigen. Initially he was treated with 4,000 rads of radiation(200 rad per day for 20 successive days), and after two months 2,500 rads of radiation(500 rad per day for 5 successive days). Three months after radiotherapy, skin lesions were healed leaving hyperpigmentation.

A Case of Lichenoid Drug Eruption Caused By Antituberculosis Drugs / 대한피부과학회지

Lichenoid drug eruption is lichenoid skin eruptions caused by certain drugs and compounds, and can be similar to lichenoid planus. A 59-year-old man who had taken antituberculosis drugs(Isoniazid, Rifampin, Ethambutol, Pyrazinamide) for 2months developed pruritic erythematous papules and plaques with silvery scales on the face, trunk and extremities. Histopathologic findings were hyperkeratosis, parakeratosis, hypergranulosis, band like lymphohistiocytic infiltration in the upper dermis and perivascular lymphohistiocytic infiltration in the deep dermis. He was treated with antihistamines and topical corticosteroid and then skin lesions slightly improved. 1 month after the termination of antituberculosis medication, skin lesions improved leaving hyperpigmentation.