Expression In Skin Tissue Research Articles

Angiopoietin-like Protein 2 Accelerates Carcinogenesis by Activating Chronic Inflammation and Oxidative Stress

Chronic inflammation has received much attention as a risk factor for carcinogenesis. We recently reported that Angiopoietin-like protein 2 (Angptl2) facilitates inflammatory carcinogenesis and metastasis in a chemically induced squamous cell carcinoma (SCC) of the skin mouse model. In particular, we demonstrated that Angptl2-induced inflammation enhanced susceptibility of skin tissues to "preneoplastic change" and "malignant conversion" in SCC development; however, mechanisms underlying this activity remain unclear. Using this model, we now report that transgenic mice overexpressing Angptl2 in skin epithelial cells (K14-Angptl2 Tg mice) show enhanced oxidative stress in these tissues. Conversely, in the context of this model, Angptl2 knockout (KO) mice show significantly decreased oxidative stress in skin tissue as well as a lower incidence of SCC compared with wild-type mice. In the chemically induced SCC model, treatment of K14-Angptl2 Tg mice with the antioxidant N-acetyl cysteine (NAC) significantly reduced oxidative stress in skin tissue and the frequency of SCC development. Interestingly, K14-Angptl2 Tg mice in the model also showed significantly decreased expression of mRNA encoding the DNA mismatch repair enzyme Msh2 compared with wild-type mice and increased methylation of the Msh2 promoter in skin tissues. Msh2 expression in skin tissues of Tg mice was significantly increased by NAC treatment, as was Msh2 promoter demethylation. Overall, this study strongly suggests that the inflammatory mediator Angptl2 accelerates chemically induced carcinogenesis through increased oxidative stress and decreased Msh2 expression in skin tissue. Angptl2-induced inflammation increases susceptibility to microenvironmental changes, allowing increased oxidative stress and decreased Msh2 expression; therefore, Angptl2 might be a target to develop new strategies to antagonize these activities in premalignant tissue.

Serum Level of Interleukin-33 and Soluble ST2 and Their Association with Disease Activity in Patients with Behcet's Disease

Interleukin (IL)-33 is an important mediator of innate immunity. Behcet's disease (BD) is an autoinflammatory disorder characterized by hyperactivity of the innate immune response. We measured serum levels of IL-33 and its receptor soluble ST2 (sST2) in patients with BD to investigate their association with disease activity. Serum levels of both IL-33 and sST2 were higher in patients with BD compared with those in normal controls (IL-33: 594.48±175.04 pg/mL in BD and 224.23±56.64 pg/mL in normal controls [P=0.048], sST2: 99.01±15.92 pg/mL in BD and 23.56±3.25 pg/mL in normal controls [P<0.001]). IL-33 and sST2 expression in skin tissue, as shown by immunohistochemistry, was higher in patients with BD compared with that in the normal controls. Serum sST2 level correlated significantly with the BD currently active form (BDCAF), Iranian BD dynamic activity measure (IBDDAM), erythrocyte sedimentation rate and C-reactive protein. Multiple linear regression showed that serum sST2 was an independent factor associated with IBBDAM (regression coefficient, 0.374; P=0.004), and BDCAF (regression coefficient, 0.236; P=0.047). These results demonstrate that IL-33 and sST2 are highly expressed in patients with BD and that serum sST2 is an independent factor associated with IBDDAM and BDCAF, suggesting a potential role for sST2 as a surrogate marker of disease activity in patients with BD.

Effect of CD200 and CD200R1 expression within tissue grafts on increased graft survival in allogeneic recipients

In transgenic mice over-expressing CD200 (CD200tg) graft survival is associated with increased intra-graft expression of mRNAs for genes associated with altered T cell subset differentiation (Foxp3; TGFβ; IL-10). Grafts are rejected in recipients lacking the inhibitory receptor for CD200, CD200R1.We compared grafts of C57BL/6 skin taken from control, CD200KO, CD200tg, CD200R1KO or CD200tg.CD200R1KO C57BL/6 donor mice transplanted to control or CD200tg BALB/c recipients. Animals received either low-dose rapamycin (0.5mg/kg), which only enhanced survival in CD200tg mice, or high dose rapamycin (1.5mg/kg) which increased graft survival in all recipients. Recipient draining lymph nodes (DLNs) were analyzed at 14days post grafting in mixed leukocyte cultures (MLCs) with irradiated BL/6 or C3H/HeJ stimulator cells, assaying antigen-specific CTL at day 5. MLC responses were correlated with changes in mRNA gene expression in skin tissue harvested from the same recipients, focusing on genes altered in “graft-accepting” CD200tg recipients. Tissue histology was used to assess graft infiltrating Foxp3+ Tregs, mast cells (MCs) and their degranulation.CD200tg grafts were accepted in control but not CD200KO/CD200R1KO recipients, along with decreased degranulation in graft MCs, diminished DLN MLC responses, and augmented intragraft Foxp3, TGFβ, IL-10 and mast cell gene expression. Skin grafts from either CD200KO or CD200R1KO donors to control mice were rejected, with no change in DLN MLC responses, no altered graft gene expression from that seen using control skin grafts, and pronounced graft MC degranulation. Our data highlight a role for both graft and host CD200/CD200R expression in increased allograft survival.

Inhibitory effects of Schizandra chinensis extract on atopic dermatitis in NC/Nga mice

Context: Schizandra chinensis Baillon (SC) is traditionally used as a medicinal plant in the Orient. Recently, SC has become recognized as an adaptogen by the mainstream medical community. Phytoadaptogens influence respiratory, cardiovascular, uterus myotonic, and immune activities. Atopic dermatitis (AD) is an allergic inflammatory skin disease caused by aberrant and over-reactive immune responses.Objective: This study assessed the suppressive effect of SC extract (SCE) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD in a NC/Nga mouse model.Materials and methods: AD was induced by topically applying 0.2% DNCB to the hairless-back of NC/Nga mice for 4 weeks. Treated mice received SCE or dexamethasone after AD induction.Results: SCE markedly suppressed DNCB-induced dermatitis, as determined by a count of scratching frequency; measurement of IgE, IgM, and histamine levels in serum; and histological observation of epidermal hyperplasia and mast-cell infiltration. Additionally, SCE lessened DNCB-induced histamine receptor mRNA expression in skin tissue and the splenic expressions of interleukin (IL)-4, IL-5, and high-affinity IgE receptor B protein.Conclusion: SCE appears useful for suppression of AD, even though the active pathway(s) remain unknown.

Byakkokaninjinto prevents body water loss by increasing the expression of kidney aquaporin‐2 and skin aquaporin‐3 in KKAy mice

Byakkokaninjinto (BKN) is an herbal medicine used for the relief of diuresis, thirst and dermal pruritus that are associated with diabetes. The effects of BKN on the expression of aquaporins (AQPs) in the kidney, salivary gland and skin were investigated in order to clarify the mechanism of drug action. Seven-week-old KKAy mice were given feed containing 4.5% BKN for 4 weeks. Compared with the control group, BKN administration did not affect the blood glucose and insulin concentration. However, water intake and urine volume were significantly reduced. AQP2 protein expression in the kidney inner medullary was significantly increased after BKN administration. AQP3 mRNA and protein expression in skin tissue was significantly increased after BKN administration. However, BKN administration did not affect AQP5 mRNA expression in the salivary gland. These results suggest that BKN treatment relieves diuresis, thirst, and dermal pruritis by increasing kidney AQP2 expression and skin AQP3 expression.

Quantitative analysis of alpha 1(I) and alpha 1(III) procollagen mRNA expression in systemic sclerosis skin tissue--an in situ hybridization study.

Human alpha 1(I) and alpha 1(III) procollagen mRNA expression in skin tissue from 15 systemic sclerosis (SSc) patients and from 7 normal control subjects was quantitatively analyzed using in situ hybridization. The grains accumulating in each area, representing procollagen mRNA expression per cell, were counted. To normalize the results from each subject, the number of cells and the number of grains per cell were divided by the area of the skin specimen (in square millimeters). The number of cells per square millimeter expressing alpha 1(I) and alpha 1(III) procollagen mRNA in SSc skin was significantly elevated compared with normal control skin (both P < 0.01). The number of grains per cell per square millimeter expressing alpha 1(III) procollagen mRNA in SSc skin was also significantly elevated compared with normal control skin (P < 0.01). The relationship between procollagen mRNA expression and the histological findings in SSc was also studied. The numbers of cells and grains per cell per square millimeter expressing alpha 1(I) procollagen mRNA in fibrotic zone SSc skin were significantly elevated compared with normal control skin (both P < 0.01). The numbers of cells and grains per cell per square millimeter expressing alpha 1(III) procollagen mRNA in SSc skin were significantly elevated compared with normal control skin (both P < 0.01) and with border zone SSc skin (number of cells P < 0.01, number of grains P < 0.05). These results indicate an increase in the number of cells showing elevated expression of alpha 1(I) and alpha 1(III) procollagen mRNA, and a close relationship between alpha 1(I) and alpha 1(III) procollagen mRNA expression and the histological findings in SSc.