Expression Pattern and Immunoregulatory Roles of Galectin-1 and Galectin-3 in Atopic Dermatitis and Psoriasis.

The pathogenesis of atopic dermatitis (AD) and psoriasis (Ps) overlaps, particularly the activation of the immune response and tissue damage. Here, we evaluated galectin (Gal)-1 and Gal-3 levels, which are beta-galactoside-binding proteins with immunomodulatory functions and examined their effects on human keratinocytes stimulated with either interleukin (IL)-4 or IL-17A. Skin biopsies from AD, Ps, and control patients were evaluated using histological and immunohistochemical analyses. Six studies containing publicly available transcriptome data were individually analyzed using the GEO2R tool to detect Gal-1 and Gal-3 mRNA levels. In vitro, IL-4- or IL-17A-stimulated keratinocytes were treated with or without Gal-1 or Gal-3 to evaluate cytokine release and migration. Our findings showed different patterns of expression for Gal-1 and Gal-3 in AD and Ps skins. Densitometric analysis in skin samples showed a marked increase in the protein Gal-1 levels in Ps epidermis and in both AD and Ps dermis compared to controls. Protein and mRNA Gal-3 levels were downregulated in AD and Ps lesional skin compared with the control samples. In vitro, both galectins addition abrogated the release of IL-8 and RANTES in IL-17-stimulated keratinocytes after 24 h, whereas IL-6 release was downregulated by Gal-3 and Gal-1 in IL-4- and IL-17-stimulated cells, respectively. Administration of both galectins also increased the rate of keratinocyte migration under IL-4 or IL-17 stimulation conditions compared with untreated cells. Altogether, the immunoregulatory and migration effects of Gal-1 and Gal-3 on keratinocytes under inflammatory microenvironment make them interesting targets for future therapies in cutaneous diseases.

The Role of Galectin-9 as Mediator of Atopic Dermatitis: Effect on Keratinocytes.

Galectin-9 (Gal-9) is a beta-galactoside-binding protein with a variety of biological functions related to immune response. However, in allergic diseases, its mechanism of action is not fully understood. This study evaluates the expression pattern of Gal-9 in patients with atopic dermatitis (AD), in ovalbumin (OVA)-induced experimental atopic dermatitis (AD) in mice, as well as its effect on human keratinocytes. The skin of OVA-immunized BALB/c mice was challenged with drops containing OVA on days 11, 14-18, and 21-24. HaCaT cells were cultured in the following experimental conditions: control (growth medium only) or stimulated with TNF-α/IFN-γ, or IL-4, or IL-17 with or without Gal-9 treatment. AD was characterized by increased levels of Gal-9 in mouse and human skin, especially in the epidermis, and with a marked influx of Gal-9 positive eosinophils and mast cells compared to the control group. Gal-9 showed an immunomodulatory effect on keratinocytes by decreasing the release of IL-6 by IL-4-stimulated keratinocytes or increasing the IL-6 and RANTES levels by IL-17- or TNF-α/IFN-γ-stimulated cells, respectively. Under IL-17, Gal-9 treatment also altered the proliferation rate of cells. Overall, increased levels of Gal-9 in AD skin contribute to the control of inflammatory response and the proliferative process of keratinocytes, suggesting this lectin as a relevant therapeutic target.

The intricate role of mast cell proteases and the annexin A1-FPR1 system in abdominal wall endometriosis.

Endometriosis is a continuous and progressive disease with a poorly understood aetiology, pathophysiology and natural history. This study evaluated the histological differences between eutopic and ectopic endometria (abdominal wall endometriosis) and the expression of mast cell proteases (tryptase and chymase), annexin A1 (ANXA1) and formyl peptide receptor 1 (FPR1). Ectopic endometrium from 18 women with abdominal wall endometriosis and eutopic endometrium from 10 women without endometriosis were obtained. The endometrial samples were analysed by histopathology, immunohistochemistry and ultrastructural immunogold labeling to determine mast cell heterogeneity (tryptase and chymase positive cells) and the expression levels of ANXA1 and FPR1. Histopathological analysis of the endometriotic lesions showed a glandular pattern of mixed differentiation and an undifferentiated morphology with a significant influx of inflammatory cells and a change in mast cell heterogeneity, as evidenced by a significant increase in the number of chymase-positive cells and endogenous chymase expression. The undifferentiated glandular pattern of endometriotic lesions was positively associated with a marked increase and co-localization of ANXA1 and FPR1 in the epithelial cells. In conclusion, the co-upregulated expression of mast cell chymase and ANXA1-FPR1 system in ectopic endometrium suggests their involvement in the development of endometriotic lesions.

Histopathological detection of entry and exit holes in human skin wounds caused by firearms.

The judiciary needs forensic medicine to determine the difference between an entry hole and an exit hole in human skin caused by firearms for civilian use. This important information would be most useful if a practical and accurate method could be done with low-cost and minimal technological resources. Both macroscopic and microscopic analyses were performed on skin lesions caused by firearm projectiles, to establish histological features of 14 entry holes and 14 exit holes. Microscopically, in the abrasion area macroscopically observed, there were signs of burns (sub-epidermal cracks and keratinocyte necrosis) in the entrance holes in all cases. These signs were not found in three exit holes which showed an abrasion collar, nor in other exit holes. Some other microscopic features not found in every case were limited either to entry holes, such as cotton fibres, grease deposits, or tattooing in the dermis, or to exit holes, such as adipose tissue, bone or muscle tissue in the dermis. Coagulative necrosis of keratinocytes and sub-epidermal cracks are characteristic of entry holes. Despite the small sample size, it can be safely inferred that this is an important microscopic finding, among others less consistently found, to define an entry hole in questionable cases.

Estudo retrospectivo dos casos de Leishmaniose tegumentar Americana diagnosticados no laboratório de patologia do Hospital de Base da FAMERP nos anos de 1995-2000, com enfoque clínico e anatomopatológico / Retrospective study of America Cutaneous Leishmaniasis cases diagnosed in the Pathology Laboratory of Hospital de Base-FAMERP: a clinical and anatomophatological focus

A Leishmaniose Tegumentar Americana é uma infecção causada pelo protozoário do gênero Leishmania, e é transmitida através da picada das fêmeas dos insetos conhecidos como flebotomíneos. o objetivo desse presente estudo foi correlacionar as formas clínicas de Leishmaniose Tegumentar Americana com a resposta inflamatória tecidual e com o índice de parasitismo. Os casos selecionados, que foram diagnosticados através de biópsia da lesão, deram entrada no Laboratório de Patologia do Hospital de Base de São José do Rio Preto entre os anos de 1995 e 2000. Nós observamos que a lesão predominante foi do tipo úlcera (90 por cento), e quando houve mais de três lesões em um mesmo paciente (20 por cento), não houve formação de granulomas. Verificamos ainda que houve reação granulomatosa (40 por cento), o grau de parasitismo foi menor, sendo classificando como leve pelos parâmetros estipulados. dessa maneira, concluímos que a presença de granuloma deixa a lesão mais contida, mais superficial e com menor número de parasitas