Normal Skin Of Healthy Controls Research Articles

IL-17: a novel player in the pathogenesis of vulvar lichen sclerosus.

Vulvar lichen sclerosus (VLS) is a chronic progressive, lymphocyte-mediated inflammatory disease whose pathogenesis is complex and not fully elucidated. In the current study we have investigated for the first time the expression of interleukin-17 (IL-17) and S100A7 in lesional skin obtained from female individuals with histologically confirmed VLS. In our study we used skin biopsies obtained from female patients with histologically confirmed VLS (n = 20) and skin samples from healthy age- and gender-matched individuals (plastic surgery procedures) (n = 10) serving as controls. The tissue expressions of IL-17 and S100A7 were assessed with an immunohistochemical method. The number of cells showing IL-17 expression was significantly higher in VLS lesional skin as compared to normal skin of healthy controls (p < 0.0001). In VLS lesional skin, IL-17 was expressed in the epidermis and by cells within the inflammatory infiltrate in the upper dermis. The number of cells showing S100A7 expression was significantly higher in VLS lesional skin as compared to normal skin of healthy controls (p < 0.0001). In VLS lesional skin, S100A7 was expressed by suprabasal keratinocytes in epidermis. S100A7 was also expressed by cells within the inflammatory infiltrate in the dermis. The results of our study may suggest the involvement of IL-17 and S100A7 in the pathogenesis of VLS. The better understanding of this disease may lead to the development of novel, effective therapeutic strategies e.g. using well-known biologics IL-17 inhibitors class.

Increased expression of psoriasin (S100A7) and interleukin 17 (IL-17) in lesional skin in lichen planopilaris.

Lichen planopilaris (LPP) is an inflammatory, primary scarring alopecia, however its pathogenesis is not completely elucidated. S100A7 is a multifunctional, antimicrobial protein with proinflammatory properties. Interleukin-17 (IL-17) is implicated in the development of various autoimmune skin diseases. To determine the tissue expression of S100A7, S100A4 and IL-17 in LPP. The immunohistochemical analysis was performed on biopsy specimens obtained from individuals with histologically confirmed lichen planopilaris (n = 23), alopecia areata (AA) (n = 11), and healthy controls (n = 14). The expression was evaluated using Zeiss Axio Imager A2 light microscope. The number of cells showing S100A7 expression was significantly higher in LPP lesional skin compared to AA lesional skin (p = 0.0002) and normal skin of healthy controls (p < 0.0001). The number of cells showing IL-17 expression was significantly higher in LPP lesional skin compared to normal skin of healthy controls (p < 0.0001) and the number of cells showing IL-17 expression was significantly higher in AA lesional skin compared to normal skin of healthy controls (p < 0.0001). The number of cells showing IL-17 expression was not significantly different in LPP lesional skin and in AA lesional skin (p > 0.05). The number of cells showing S100A4 expression was not significantly different in LPP lesional skin, AA lesional skin and in normal skin of healthy controls. The results of our study suggest the possible role of S100A7 and IL-17 in the pathogenesis of LPP.

The Role of EREG, PTPN1, and SERPINB7 Genes in the Pathogenesis of Psoriasis: May SERPINB7 Be Protective and a Marker of Severity for Psoriasis?

Psoriasis is a chronic inflammatory dermatological disease with complex pathogenesis in which many immune system cells, including keratinocytes, play a role. Many genes regulate the proliferation of keratinocytes and other immune cells that have essential roles in the pathogenesis of psoriasis. The expressions of EREG, PTPN1, and SERPINB7 genes were shown as upregulated in psoriatic skins in a few studies previously. We aimed to evaluate the expressions of these genes in psoriatic lesional skin and compared them with non-lesional adjacent skin of the same patients and normal skin of healthy controls. Our results revealed that the expressions of EREG and PTPN1 genes were upregulated, whereas the SERPINB7 gene expression was down regulated in the psoriatic skin of the patients than normal skin of controls. Moreover, the expression level of the SERPINB7 gene was also negatively correlated with the severity of the disease among patients. According to our results, overexpression of EREG and PTPN1 genes, and decreased expression of SERPINB7 gene may lead to the development of psoriasis.

The role of LncRNA MALAT-1 and MiRNA-9 in Psoriasis

BackgroundPsoriasis is a chronic skin disorder manifested by recurrent episodes of scaly, red, itchy skin patches that occur within apparently normal skin. ObjectivesThis study was performed to detect the expression of serum and tissue (lesion and non-lesion) LncRNA MALAT-1 and MiRNA-9 that might be used as biomarkers for psoriasis. MethodsBlood samples were obtained from 60 psoriasis patients and 40 controls, as well as 4 mm punch biopsy from lesional and non lesional skin of psoriatic patient and normal skin of healthy controls. Expression of LncRNA MALAT-1 and miRNNA-9 in serum and tissues was detected by real time qRT-PCR. Resultsa statistically significant increase in the expression of MALAT-1 in lesional and non-lesional skin and serum of psoriatic patients in comparison to controls were detected. Moreover, there was statistically significant increase in serum MiRNA-9 in patients in comparison to controls, while its tissue level was significantly lower in patients. ConclusionThis study highlights the dysregulation of LncRNA MALAT-1 and miRNA-9 in psoriasis. Elevated expression of MALAT-1 in lesional skin of psoriatic patients compared to non-lesional skin may possibly contribute to the development of psoriatic plaques.

Production of IL-31 in CD45RO+CLA+H4R+ T Cells in Atopic Dermatitis.

IL-31 is involved in pruritus in atopic dermatitis (AD) and the pathogenesis of AD. However, the mechanism of IL-31 production is not fully understood. We sought to investigate the association between CD45RO+CLA+H4R+ T cells and IL-31 production. Immunofluorescence studies were performed retrospectively on punch-biopsy specimens from five people with AD and three healthy controls. In addition, blood samples were collected prospectively from eight patients with AD and eight healthy controls for sorting CD45RO+CLA+H4R+ T cells. There was no overlap of patients between the biopsy group and the blood sampling group. Sorted cells were stimulated with 4-methylhistamine (4MH), and the level of IL-31 was measured by an enzyme-linked immunosorbent assay. Immunofluorescence showed co-localization of H4R and IL-31 in lesional AD skin but not in normal skin of healthy controls. The proportion of CLA+H4R+ T cells among CD3+CD45RO+ lymphocytes was 18.3 ± 6.2% in patients with AD and 11.2 ± 7.6% in healthy controls. In the AD group, production of IL-31 by CD45RO+CLA+H4R+ T cells increased from 32.4 ± 13.3 pg/mL to 47.5 ± 18.7 pg/mL by 4MH stimulation after 24 h (p < 0.001). However, in the control group, production of IL-31 was 20.1 ± 10.6 pg/mL without and 22.1 ± 9.3 pg/mL with 4MH stimulation (p > 0.05). According to our study, CD45RO+CLA+H4R+ T cells are an important source of IL-31 in AD, and may be a target for treatment of IL-31-induced pruritus.

Lysyl oxidase-like-2 mutations and reduced mRNA and protein expression in mid-dermal elastolysis.

Mid-dermal elastolysis (MDE) is a rare skin condition, characterized by selective loss of elastic fibres in the mid dermis. The pathogenesis of MDE is still unclear. To investigate expression of lysyl oxidase-like 2 (LOXL2) in a reasonable sample of patients with MDE and to search for mutations in LOXL2. We investigated archived lesional tissue of 13 patients with MDE and skin tissue samples of 10 sex- and age-matched healthy controls (HCs). Gene and protein expression of LOXL2 was investigated using real-time reverse-transcription PCR and immunohistochemistry. Mutation analysis was performed using the Sanger method. We observed decreased LOXL2 mRNA expression in lesional skin of patients with MDE (0.48±0.16) compared with healthy skin of the same patients (1.5±0.51) and normal skin of HCs (1.9±0.13). Compared with healthy patient skin (epidermis 2.38±1.6, dermis 1.2±1), LOXL2 protein expression in lesional patient skin (epidermis 1.1±0.7, dermis 0.3±0.45) was significantly decreased (P<0.04 and P=0.02, respectively). Mutation analysis of the entire LOXL2 gene could be performed for five patients, all of whom were found to have at least one mutation in the LOXL2 gene. Three of these had a mutation in the promoter region (c.967 G>C, c.1022 C>T, and c.1025 G>A, respectively), and one of them also had a mutation in the splice region of intron 11/exon 12 (IVS11-1 G>A). Of the remaining two patients, one had a mutation in exon 3 (T1391), and the other had a mutation in exon 11 (C663Y). Our present data suggest that decreased elastin renewal due to LOXL2 mutations and consecutive reduced LOXL2 expression contribute to the pathogenesis of MDE.

MicroRNAs in cutaneous lichen planus.

Lichen planus (LP) is a chronic, inflammatory, papulosquamous, autoimmune disease. The pathogenesis of LP appears to be complex, with interactions between genetic, environmental and lifestyle factors. MicroRNAs (miRNAs) are short RNAs encoded in both protein coding and noncoding areas of the genome, and have been found to be involved in the pathogenesis of some inflammatory skin diseases. The aim of this study was to map the levels of miRNA (miR-)-203 and miR-125b in cutaneous LP to evaluate their possible role in the pathogenesis of the disease. In total, 40 patients with classic cutaneous LP and 40 age- and sex- matched healthy controls (HCs) were enrolled in this study. Punch biopsies (4 mm) were taken from cutaneous LP lesions of patients and from normal skin of HCs. miRNA-203 and miRNA-125b mRNA expression was estimated by reverse transcription PCR. Our analysis revealed a significantly (P < 0.001 for both) lower expression of both miR-203 and miR-125b mRNA in the LP than in the HC biopsies. No relationship was found between expression of miR-203 or miR-125b and either age, sex, presence of mucosal lesions or positivity for HCV antibodies. miR-125b and miR-203 could be involved in the pathogenesis of cutaneous LP.

Mutation analysis of the nicastrin gene in a Chinese pedigree with acne inversa

Objective To identify mutations of the γ-secretase gene in two patients with acne inversa (AI)in a Chinese pedigree. Methods Blood samples were obtained from 5 family members (including 2 patients, the proband's father, 2 unaffected family members)and 100 unrelated healthy controls. Genomic DNA was extracted from these blood samples, and PCR was conducted to amplify all the exons and their flanking sequences of nicastrin (NCSTN), presenilin-1 (PSEN1), presenilin enhancer (PSENEN)and anterior pharynx-defective 1 (APH1)genes, followed by direct sequencing. Besides, the NCSTN mRNA expression in skin lesions of the proband was compared with that in the normal skin of 4 healthy controls. Results A heterozygous mutation (c.477C > A)at position 477 in the exon 5 of the NCSTN gene, which had not been described previously in the National Center for Biotechnology Information (NCBI)single nucleotide polymorphism database, was identified in the 2 patients, but not observed in the other 3 unaffected family members or the 100 unrelated controls. Additionally, the mRNA expression of NCSTN was evidently decreased in the lesions of the proband compared with the normal skin of healthy controls. Conclusion The novel nonsense mutation c.477C> A in the NCSTN gene is the causative mutation of AI in this family, and it may induce functional inactivation of NCSTN through the nonsense-mediated mRNA decay. Key words: Acne inversa; Genes; Mutation; Pedigree; Genes, nicastrin

Upregulation of human β-defensin-3 and cathelicidin LL-37 in Kaposi’s sarcoma

Background: Kaposi’s sarcoma (KS) is a rare neoplasm of lymphatic endothelial cells. Human herpes virus 8 (HHV-8) is considered to be a necessary, but not sufficient causal agent of KS and additional cofactors remain unknown. In this study we evaluated the expression of human β defensin (HBD)-3 and LL-37 in cutaneous lesions of KS in comparison to the healthy skin of normal subjects. Methods: We performed a quantitative immunohistochemical study of HBD-3 and LL-37 on skin lesions from 18 patients having KS, and on healthy skin from 12 normal controls. Results: HBD-3 and LL-37 were significantly upregulated in epidermal and dermal specimens of all KS patients in comparison to normal skin of healthy controls. The immunostaining score of dermal HBD-3 was significantly higher in nodular lesions (9.6 &plusmn; 2.4) versus plaque lesions (4.1 &plusmn; 2.2), P = 0.001. Also the immunostaining score of dermal LL-37 was significantly higher in nodular lesions versus plaque lesions (P = 0.001). Conclusions: We have demonstrated for the first time that HBD-3 and LL-37 are significantly upregulated in lesional skin of KS in comparison to the skin of healthy controls. The obtained data suggest a possible involvement of these antimicrobial peptides in the pathogenesis of KS. However, the biological significance of HBD-3 and LL-37 in KS lesions needs further research.

Upregulation of human β-defensin-3 and cathelicidin LL-37 in Kaposi’s sarcoma

Background: Kaposi’s sarcoma (KS) is a rare neoplasm of lymphatic endothelial cells. Human herpes virus 8 (HHV-8) is considered to be a necessary, but not sufficient causal agent of KS and additional cofactors remain unknown. In this study we evaluated the expression of human β defensin (HBD)-3 and LL-37 in cutaneous lesions of KS in comparison to the healthy skin of normal subjects. Methods: We performed a quantitative immunohistochemical study of HBD-3 and LL-37 on skin lesions from 18 patients having KS, and on healthy skin from 12 normal controls. Results: HBD-3 and LL-37 were significantly upregulated in epidermal and dermal specimens of all KS patients in comparison to normal skin of healthy controls. The immunostaining score of dermal HBD-3 was significantly higher in nodular lesions (9.6 ± 2.4) versus plaque lesions (4.1 ± 2.2), P = 0.001. Also the immunostaining score of dermal LL-37 was significantly higher in nodular lesions versus plaque lesions (P = 0.001). Conclusions: We have demonstrated for the first time that HBD-3 and LL-37 are significantly upregulated in lesional skin of KS in comparison to the skin of healthy controls. The obtained data suggest a possible involvement of these antimicrobial peptides in the pathogenesis of KS. However, the biological significance of HBD-3 and LL-37 in KS lesions needs further research.

Upregulation of human β-defensin-3 and cathelicidin LL-37 in Kaposi’s sarcoma

Background: Kaposi’s sarcoma (KS) is a rare neoplasm of lymphatic endothelial cells. Human herpes virus 8 (HHV-8) is considered to be a necessary, but not sufficient causal agent of KS and additional cofactors remain unknown. In this study we evaluated the expression of human β defensin (HBD)-3 and LL-37 in cutaneous lesions of KS in comparison to the healthy skin of normal subjects. Methods: We performed a quantitative immunohistochemical study of HBD-3 and LL-37 on skin lesions from 18 patients having KS, and on healthy skin from 12 normal controls. Results: HBD-3 and LL-37 were significantly upregulated in epidermal and dermal specimens of all KS patients in comparison to normal skin of healthy controls. The immunostaining score of dermal HBD-3 was significantly higher in nodular lesions (9.6 &plusmn; 2.4) versus plaque lesions (4.1 &plusmn; 2.2), P = 0.001. Also the immunostaining score of dermal LL-37 was significantly higher in nodular lesions versus plaque lesions (P = 0.001). Conclusions: We have demonstrated for the first time that HBD-3 and LL-37 are significantly upregulated in lesional skin of KS in comparison to the skin of healthy controls. The obtained data suggest a possible involvement of these antimicrobial peptides in the pathogenesis of KS. However, the biological significance of HBD-3 and LL-37 in KS lesions needs further research.