Polymorphisms of tumor necrosis factor (TNF) α and β genes in Korean patients with psoriasis

To evaluate the association of TNF-alpha (TNFA) and TNF-beta (TNFB) polymorphisms with psoriasis in the Korean population, we investigated TNF-alpha -238 and -308 promoter region and TNF-beta NcoI polymorphism using PCR-RFLP in 103 Korean psoriasis patients and 125 normal controls. The carriage and allele frequencies of TNFB*2 were significantly increased in patients with psoriasis compared with normal controls. However, TNFB*1/1 homozygote and TNFB*1 allele were significantly decreased in the patients. There were no significant differences in the polymorphism of TNF-alpha promoter -238 and -308 between the patients and controls. We also analyzed the frequencies of TNFB alleles according to the clinical characteristics of the psoriasis patients, but no significant differences were found. However, female patients with early-onset psoriasis showed an association with the TNFB*2 allele. In conclusion, our results suggest that polymorphisms of the TNFB gene may contribute to a predisposition to psoriasis in the Korean population.     

Serum TNF-α in psoriasis after treatment with propylthiouracil,an antithyroid thioureylene

Background  

Tumor necrosis factor-α (TNF-α) and its receptors play important roles in the development and persistence of psoriatic plaques. The antithyroid thioureylenes, propylthiouracil and methimazole, are effective in the treatment of patients with psoriasis with a significant number of patients showing clearing or near clearing of their lesions after a several weeks of treatment.     

Inflammatory linear verrucous epidermal nevus (ILVEN) and psoriasis in a child?

A male infant, whose father was affected by psoriasis, was first seen in our department at 1 month of life for a “bipolar” seborrheic dermatitis, that resolved without treatment at 7 months of age. At 15 months of life, the child returned for an eruption of erythematous and finely scaling papules disposed in a linear, band‐like fashion over the left part of the body, involving the volar surface of the arm, the left leg from the inguinal fold to the ankle, and the abdomen and thorax, where they assumed the typical S‐shaped curve following Blaschko lines. The lesions were not itchy. A punch biopsy of a linear lesion on the left arm was performed. Histopathologic examination showed parakeratosis with absence of the granular layer, mild acanthosis with papillomatosis, necrosis of single keratinocytes, and a mild lymphohistiocytic infiltrate located in the superficial dermis. A tentative diagnosis of lichen striatus was made. After a few days, a diffuse eruption of pinpoint‐sized, lenticular, erythemato‐desquamative lesions occurred on the trunk and limbs, with the typical clinical appearance of guttate psoriasis ( Fig. 1 ). The child was in good general condition, and routine blood tests were within the normal range. No triggering factor was found. Treatment with emollients led to the resolution of the psoriatic lesions within 4 months; in contrast, the linear lesions were not grossly changed by this treatment and just appeared more flattened.

Figure 1 Open in figure viewer PowerPoint At 15 months of life: scaling papules disposed in a linear band over the left part of the body and diffuse lenticular erythemato‐desquamative lesions     

Elevated levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-10 in hidradenitis suppurativa skin: a rationale for targeting TNF-α and IL-1β

Background The pathogenesis of hidradenitis suppurativa (HS) is largely unknown and the disease is difficult to treat. Patients are in high need of an effective treatment. Although it is not known whether the levels of tumour necrosis factor (TNF)‐α are aberrant in HS skin, anti‐TNF‐α biologics are used, with variable clinical efficacy. Objectives To determine the cytokine profile in lesional and perilesional HS skin. Methods We cultured 20 lesional and 10 normal‐appearing perilesional HS skin samples, seven psoriasis and six healthy control skin samples in a transwell culture system. Two distinct cytokine bead arrays were used to measure the spectrum of inflammatory cytokines in the culture supernatant. Results from HS skin samples were compared with those of healthy and psoriasis skin. Results The proinflammatory cytokines interleukin (IL)‐1β and TNF‐α as well as the anti‐inflammatory cytokine IL‐10 were significantly elevated in HS skin. Elevated levels of these cytokines were also found in perilesional HS skin. Fold increases relative to control skin of IL‐1β, TNF‐α and IL‐10 in HS were 31, 5 and 34, compared with psoriasis: 4, 1 and 2, respectively. Levels of all three cytokines showed a trend towards a positive correlation with disease severity. IL‐2, IL‐4, IL‐5 and interferon‐γ were hardly detectable in HS or healthy control skin. Conclusions This study shows for the first time that IL‐1β, TNF‐α and IL‐10 levels are elevated in HS skin. These data provide a rationale for therapies with biologics targeting cytokines such as TNF‐α and IL‐1.     

Genetic variations in the genes encoding receptor activator nuclear factor κ B (RANK), receptor activator nuclear factor κ B ligand (RANKL) and osteoprotegerin (OPG) in patients with psoriasis and psoriatic arthritis: a case-control study

Psoriasis (Ps) and psoriatic arthritis (PsA) are diseases of unknown origin. However, the receptor activator nuclear factor κ B ligand (RANKL) might play a key role in the pathomechanisms of the disease. Our aim was to study seven single nucleotide polymorphisms (SNP) in the genes encoding for receptor activator nuclear factor κ B (RANK, two SNP), osteoprotegerin (OPG, two SNP) and RANKL (three SNP in patients with Ps and PsA). A case-control study with 156 Ps patients (45 with PsA) and 516 healthy blood donors was conducted to evaluate an association of the SNP with Ps and PsA by genotyping of DNA by polymerase chain reaction. None of the seven SNP showed any differences in the allelic or genotype frequencies between Ps patients and controls. Our study showed no significant association between the SNP in the genes encoding for RANK, OPG and RANKL with susceptibility of disease in Ps and PsA patients.     

Interleukin-1 Gene Polymorphisms and their Relation with NFκB Expression and Histopathological Features in Psoriasis

Background:

Psoriasis is a chronic inflammatory disease driven by exaggerated production of pro-inflammatory cytokines and interleukins. Various genetic polymorphisms including IL-1 are implicated in pathogenesis of psoriasis. The exact role of IL-1 gene polymorphisms and their interaction with NFκB is not yet determined. We aimed to study various genetic polymorphisms of IL-1 in psoriasis and their influence on NFκB and histopathological features.

Materials and Methods:

112 newly diagnosed cases of psoriasis vulgaris were included in this prospective study. Histology was done on sections and genotyping was done for the IL-1β and IL-1 receptor antagonist (IL-1RA) genetic polymorphisms. In addition, NFκB immunostaining was performed on 89 sections and the intensity of staining was evaluated in the epidermis, basal cells, and the lymphocytes.

Results:

A strong association of IL-1β 511 C/T polymorphism was found with both genotypes and alleles in psoriasis. A strong correlation was also detected between the IL-1β genotype and the grade of NFκB immunostaining in the epidermis (P = 0.012). The grade of NFκB lymphocyte staining showed a strong correlation with the IL-1RA genotype (P = 0.025) but not with the IL-1β genotype (P = 0.226). The genetic polymorphisms did not show any correlation with the histological features.

Conclusions:

IL-1 genetic polymorphisms may not play a very direct role in pathogenesis of psoriasis. However, their interaction with NFκB appears to be a significant factor in this direction as NFκB is activated by pro-inflammatory genetic polymorphisms and therefore may influence the severity of psoriasis.     

Expression Patterns of Gli-1, Pleckstrin Homology-Like Domain,Family A,Member 1, Transforming Growth Factor-β1/β2, and p63 in Sebaceous and Follicular Tumors

Background

Certain epidermal appendage tumors, including hyperplasias (hamartomas), adenomas, benign epitheliomas, primordial epitheliomas, and malignant tumors, can exhibit any stage of differentiation. Several molecules associated with tumorigenesis, such as Gli-1, pleckstrin homology-like domain, family A, member 1 (PHLDA-1), transforming growth factor (TGF)-β1, TGF-β2, and p63, are associated with tumor grade and aggressive behavior in follicular and sebaceous tumors in ways that are not well understood.

Objective

The aim of this study was to elucidate the expression of Gli-1, PHLDA-1, TGF-β1/β2, and p63 in benign and malignant tumors of the hair and sebaceous glands and to determine their importance in the degree of tumor differentiation.

Methods

Immunohistochemistry was performed in follicular and sebaceous tumors using antibodies against Gli-1 (sebaceous tumor marker), PHLDA-1 (hair follicle outer root sheath [ORS] cell marker), p63, TGF-β1, and TGF-β2.

Results

Gli-1 was expressed in basaloid cells, sebocytes, and sebaceous carcinoma cells, and expression levels decreased as differentiation progressed. PHLDA-1 was expressed in ORS cells and some follicular tumor cells. Expression of p63 was observed in the nuclei of the outermost basaloid cells (seboblasts), poorly differentiated sebaceous carcinoma cells, and tumor cells toward the direction of the hair. Remarkably, TGF-β1 was expressed exclusively in the nuclei of benign and malignant follicular (hair) tumors, but not in sebaceous tumors, at levels that correlated with the degree of differentiation.

Conclusion

We propose that p63 and/or TGF-β1 are useful for predicting the degree of differentiation and malignant potential of sebaceous and follicular tumors and for distinguishing trichilemmal carcinoma from sebaceous carcinoma.     

How do personality systems interact in patients with psoriasis, atopic dermatitis and urticaria?

The aim of this study was to evaluate characteristic personality system interaction in patients with psoriasis, atopic dermatitis and urticaria. The differences between these three disease groups were examined with respect to various psychological variables and deviations from a group of healthy controls. A total of 56 patients with atopic dermatitis (n=21), psoriasis (n=20) and urticaria (n=15) were tested with the "Assessment of Personality Functioning in Therapy" Inventory, which consists of psychometric scales for basic needs (affiliation, achievement, power), enactment of needs-related behaviour, stress, emotional dispositions, cognitive styles and various self-regulation functions. Significant differences with respect to needs and motivational goals, cognitive styles and self-regulation competence were found between the three disease groups, showing considerable overlap between atopic dermatitis and urticaria, but only a little overlap with psoriasis. From a psychological viewpoint, patients with psoriasis seem to carry a higher risk of developing mental disorders. Based on our results, existing prevention programmes for patients with atopic dermatitis seem appropriate, whereas such programmes for patients with psoriasis should focus on self-motivation, prevention of addictive behaviour, and strengthening of self-efficacy.     

TGF-β1 up-regulates transglutaminase two and fibronectin in dermal fibroblasts: a possible mechanism for the stabilization of tissue inflammation

Transglutaminase (TGase) has been reported to stabilize tissue inflammation via the mediation of the polymerization of extracellular matrix proteins. A set of cytokines has been implicated in wound healing processes in the dermis. This study was undertaken in order to evaluate the effects of these cytokines on the expression of TGase 2 in human dermal fibroblasts (hDFs), in that TGase 2 is known to be the principal TGase in the dermis. In Western blot analysis, TGF-β1 (1 ng/ml) treatment was found to steadily up-regulate TGase 2 expression for up to 7 days. However, such increases were not observed when the cells were treated with IL-1β, IL-2, and TNF-α. In the enzyme assay, total TGase activities were closely related to the levels of TGase 2 expression. TGase 2 mRNA expression was up-regulated as the result of TGF-β treatment in competitive RT-PCR. In the denatured SDS-PAGE, TGF-β1 treatment resulted in marked induction of an approximately 220 kDa protein, which was revealed to be a fibronectin (FN) via western immunoblotting with an anti-FN antibody. Next, when the hDFs were treated with TGF-β1 (1 ng/ml), FN expression was induced beginning at the third day after treatment. The immunoprecipitants generated by anti-FN antibody were positive for the anti-TGase 2 antibody, and the immune complexes were identified at molecular weights of 92 kDa. Collectively, TGF-β1 stimulates the polymerization of FN via the action of TGase 2, which is supposed to to be an important mechanism in the stabilization of the inflammatory dermis.