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Zhang S.,Fudan University | Yu N.,Shanghai Skin Disease Hospital | Zhang R.,Fudan University | Wu J.,Fudan University
Investigative Ophthalmology and Visual Science

PURPOSE. Inflammasome activation and IL-1β production have been proposed to have an important role in age-related macular degeneration (AMD). Growing evidence is emerging for involvement of interleukin-17A (IL-17A) in AMD pathogenesis. We investigated the effects of IL-17A on the activation of inflammasome and production of IL-1β in primary human RPE cells. METHODS. Primary human RPE cells were isolated and cultured for the following experiments. Expression patterns of IL-17 receptor A (IL-17RA), IL-17 receptor C (IL-17RC), and ACT1 were analyzed by RT-PCR, flow cytometry, and immunofluorescence. IL-17A was added to the cell cultures, and cytokine expression, signaling pathways, and inflammasome machinery were investigated using real-time RT-PCR, ELISA, Western blot, flow cytometry, and small interfering RNA. RESULTS. Retinal pigment epithelial cells constitutively expressed IL-17RA, IL-17RC, and ACT1. IL-17A upregulated the mRNA levels of pro-IL-1β, IL-8, CCL2, and CCL20, as well as the protein level of IL-1β. IL-17A induced the phosphorylation of Akt, Erk1/2, p38 MAPK, and NFjB p65 in RPE cells. Blocking NF-jB attenuated IL-17A–induced expression of pro-IL-1β mRNA. IL-17A enhanced pro-caspase-1 and NLRP3 mRNA expression. Inhibiting caspase-1 activity and silencing NLRP3 decreased IL-1b secretion, confirming NLRP3 as the IL-17A– responsive inflammasome on the posttranscriptional level. The mechanism of IL-17A– triggered NLRP3 activation and subsequent IL-1β secretion was found to involve the generation of reactive oxygen species. CONCLUSIONS. Our results suggest that IL-17A triggers a key inflammatory mediator, IL-1β, from RPE cells, via NLRP3 inflammasome activation, holding therapeutic potential for AMD. © 2016. Sci all right reserved. Source

Zhang S.,Fudan University | Yu N.,Shanghai Skin Disease Hospital | Xiang L.,Fudan University
Archives of Dermatological Research

Intercellular adhesion molecule-1 (ICAM-1) expression has been detected in melanocytes around active vitiligo patches as well as in surgically transplanted melanocytes. However, it is unclear whether and how skin injury induces the inappropriate expression of ICAM-1 and other proinflammatory genes in melanocytes. We previously reported that human melanocytes expressed TLR3. We hypothesized that the TLR3 expressed in melanocytes may recognize skin injury by binding to the endogenous ligands secreted by the damaged keratinocytes. Here we showed that RNA released from necrotic keratinocytes induced the upregulation of ICAM-1 protein and mRNA, as shown by FACS and real-time RT-PCR. Use of NF-κB inhibitor prevents upregulation of ICAM-1 in melanocytes indicating a direct role of NF-κB in necrotic keratinocyte-mediated upregulation of ICAM-1. Using a shRNA-expressing lentivirus, we demonstrated that in human melanocytes, TLR3 seems to be necessary for the upregulation of ICAM-1. Using oligonucleotide microarray, we demonstrated a dramatic increase in proinflammatory cytokine and chemokine transcripts (CXCL10, CXCL11, TNFSF10, CCL5, CCL4, CCL2, IFNB1, CCL20, IL-8, and CCL11). These observations suggested that RNA released from necrotic keratinocytes might act as an endogenous TLR3 ligand for the stimulation of ICAM-1 and other proinflammatory gene expression in human melanocytes, which might be involved in the pathogenesis of vitiligo following skin physical trauma. © 2011 Springer-Verlag. Source

Gao Y.,Anhui Medical University | Wang X.,Shanghai Skin Disease Hospital | Chen S.,Shanghai University | Li S.,Tongji University | Liu X.,Anhui Medical University
Skin Research and Technology

Purpose: To establish a model of standardized acute barrier disruption, investigate the response of normal human to repeated tape stripping, and analyze the change of damaged skin with non-invasive examination techniques for skin, such as TEWL and squamometry. Methods: Repeated tape stripping with corneofix was applied on three different anatomical sites; the measurement of TEWL was performed on the baseline and after every 5 strips. Then, the samples of corneofix were analyzed using Visioscan® VC98 and squamometry. Results: The parameter of TEWL and cohesion score show stable change trend. TEWL increased with frequency of stripping and were significantly higher compared with that of baseline on three sites. The results of staining of corneofix showed that the intercorneocyte cohesion is increased with the number of strips, and the more the number of strips, the more the fixation of dye per cell. Conclusion: The changes in the skin barrier function of different sites were different after it accepted physical stimulation, the process of damaging skin barrier could be divided into three stages based on the △TEWL. In addition, through stripping the skin of an adult, the in vivo model of damaged skin barrier could be setup. © 2012 John Wiley & Sons A/S. Source

Liu N.,Shanghai Skin Disease Hospital | Wang X.,Shanghai Skin Disease Hospital | Odio M.,Procter and Gamble
Pediatric Dermatology

Chinese cloth diapers differ from disposable diapers in several respects that are central to our understanding of the etiology of diaper dermatitis (DD), yet there are no published reports on the dermatological correlates of this manner of infant care, which is prevalent among the world's second-largest pediatric population. The objective was to determine the prevalence and severity of DD in exclusive users of Chinese cloth diapers. This observational study was conducted during a single home visit to 694 Chinese children who were exclusive users of cloth diapers in five inland cities of China. During each home visit, study nurses documented the presence and severity of DD using a visual dermatological scale and conducted transepidermal water loss (TEWL) and pH measurements. Diaper dermatitis was rare in the buttocks and genital area of the children (<20%) but was common in the perianal and intertriginous regions (50-70%). TEWL and pH were mildly higher in babies with DD than in those without DD in the genital and buttocks area. Diaper dermatitis is common in children who use traditional Chinese cloth diapers, especially in the perianal and intertriginous regions. © 2011 Wiley Periodicals, Inc. Source

Gu W.,Shanghai Skin Disease Hospital | Yang Y.,Shanghai Skin Disease Hospital | Wu L.,Shanghai Skin Disease Hospital | Yang S.,Shanghai Skin Disease Hospital | Ng L.-K.,Public Health Agency of Canada
BMJ Open

Objective: In this study, we aimed to determine the performance characteristics of toluidine red unheated serum test on cerebrospinal fluids (CSF-TRUST) as compared to venereal disease research laboratory test on cerebrospinal fluids (CSF-VDRL) for laboratory the diagnosis of neurosyphilis. Design: A cross-sectional study. Setting: Sexually transmitted infections (STIs) clinics. Participants and methods: CSF and serum samples were collected from 824 individual STD clinic patients who have syphilis and are suspected to progress to neurosyphilis within a 9-month period. CSF-VDRL and CSF-TRUST were performed parallelly on the same day when collected. Treponema pallidum particle agglutination (TPPA) tests were also performed on the CSF and the serum samples, and biochemical analysis of the CSF samples was also performed. Results: The overall agreement between CSF-TRUST and CSF-VDRL was 97.3%. The reactive ratios of the CSF samples were 22.1% by CSF-TRUST and 24.8% by CSF-VDRL, respectively. All CSF-TRUST-reactive cases were reactive in the CSF-VDRL. Twenty-two samples with CSF-TRUST-negative were tested CSFVDRL- reactive with low titres (1 : 1 to 1 : 4). Over 97% of the double-reactive CSF samples (CSF-VDRL and CSF-TRUST) had an identical titre or a titre within a two-fold difference. The agreement of CSF-TPPA and CSF-VDRL was 71.9%. Similarly, the agreement of CSF-TPPA and CSF-TRUST was 69.2%. Conclusions: Our results revealed that CSF-TRUST could be used as an option for CSF examination in settings without CSF-VDRL in place. Source

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