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

Effects of Formyl Peptide Receptor Agonists Ac_9-12 and WKYMV in In Vivo and In Vitro Acute Inflammatory Experimental Models

Formyl peptide receptors (Fprs) are a G-protein-coupled receptor family mainly expressed on leukocytes. The activation of Fpr1 and Fpr2 triggers a cascade of signaling events, leading to leukocyte migration, cytokine release, and increased phagocytosis. In this study, we evaluate the effects of the Fpr1 and Fpr2 agonists Ac9-12 and WKYMV, respectively, in carrageenan-induced acute peritonitis and LPS-stimulated macrophages. Peritonitis was induced in male C57BL/6 mice through the intraperitoneal injection of 1 mL of 3% carrageenan solution or saline (control). Pre-treatments with Ac9-12 and WKYMV reduced leukocyte influx to the peritoneal cavity, particularly neutrophils and monocytes, and the release of IL-1β. The addition of the Fpr2 antagonist WRW4 reversed only the anti-inflammatory actions of WKYMV. In vitro, the administration of Boc2 and WRW4 reversed the effects of Ac9-12 and WKYMV, respectively, in the production of IL-6 by LPS-stimulated macrophages. These biological effects of peptides were differently regulated by ERK and p38 signaling pathways. Lipidomic analysis evidenced that Ac9-12 and WKYMV altered the intracellular lipid profile of LPS-stimulated macrophages, revealing an increased concentration of several glycerophospholipids, suggesting regulation of inflammatory pathways triggered by LPS. Overall, our data indicate the therapeutic potential of Ac9-12 and WKYMV via Fpr1 or Fpr2-activation in the inflammatory response and macrophage activation

Comércio internacional de serviços e complexo industrial da saúde: implicações para os sistemas nacionais de saúde International trade in health services and the medical industrial complex: implications for national health systems

Os serviços de saúde evidenciam um padrão de inovação - na forma de expansão para mercados públicos e do comércio internacional - que os credencia a assumir um papel preponderante no complexo industrial da saúde. O comércio internacional e suas bases regulatórias, definidas no General Agreement on Trade in Services (GATS), têm o potencial de gerar desenvolvimento econômico, mas também de reordenar os recursos disponíveis para a saúde em âmbito nacional e global, em direções favoráveis ou não. Onde houver uma combinação de prestadores públicos e privados atuando na saúde pública, como no caso brasileiro, os termos do GATS admitem a interpretação de que a prestação pública recai no âmbito do GATS, criando-se restrições às opções políticas dos países para a saúde. São necessárias informações sistematizadas e específicas para cada país sobre serviços eletrônicos, movimento de pacientes e profissionais, e investimento direto estrangeiro em serviços de saúde para compor evidências que permitam decisões mais informadas sobre adesão ao GATS.<br>Health services have increasingly proven to be an innovative sector, gaining prominence in the medical industrial complex through expansion to public and international markets. International trade can foster economic development and redirect the resources and infrastructure available for healthcare in different countries in favorable or unfavorable directions. Wherever private providers play a significant role in government-funded healthcare, GATS commitments may restrict health policy options in subscribing countries. Systematic information on the impacts of electronic health services, medical tourism, health workers' migration, and foreign direct investment is needed on a case-by-case basis to build evidence for informed decision-making, so as to maximize opportunities and minimize risks of GATS commitments