IL-33 promotes ST2-dependent lung fibrosis by the induction of alternatively activated macrophages and innate lymphoid cells in mice

Background<p></p> The initiation and regulation of pulmonary fibrosis are not well understood. IL-33, an important cytokine for respiratory diseases, is overexpressed in the lungs of patients with idiopathic pulmonary fibrosis.<p></p> Objectives<p></p> We aimed to determine the effects and mechanism of IL-33 on the development and severity of pulmonary fibrosis in murine bleomycin-induced fibrosis.<p></p> Methods<p></p> Lung fibrosis was induced by bleomycin in wild-type or Il33r (St2)−/− C57BL/6 mice treated with the recombinant mature form of IL-33 or anti–IL-33 antibody or transferred with type 2 innate lymphoid cells (ILC2s). The development and severity of fibrosis was evaluated based on lung histology, collagen levels, and lavage cytology. Cytokine and chemokine levels were quantified by using quantitative PCR, ELISA, and cytometry.<p></p> Results<p></p> IL-33 is constitutively expressed in lung epithelial cells but is induced in macrophages by bleomycin. Bleomycin enhanced the production of the mature but reduced full-length form of IL-33 in lung tissue. ST2 deficiency, anti–IL-33 antibody treatment, or alveolar macrophage depletion attenuated and exogenous IL-33 or adoptive transfer of ILC2s enhanced bleomycin-induced lung inflammation and fibrosis. These pathologic changes were accompanied, respectively, by reduced or increased IL-33, IL-13, TGF-β1, and inflammatory chemokine production in the lung. Furthermore, IL-33 polarized M2 macrophages to produce IL-13 and TGF-β1 and induced the expansion of ILC2s to produce IL-13 in vitro and in vivo.<p></p> Conclusions<p></p> IL-33 is a novel profibrogenic cytokine that signals through ST2 to promote the initiation and progression of pulmonary fibrosis by recruiting and directing inflammatory cell function and enhancing profibrogenic cytokine production in an ST2- and macrophage-dependent manner

Metodologia para validar IPS’s de código-fonte aberto

O presente trabalho tem por objetivo descrever uma metodologia para realizar testes com ferramentas IPS (Intrusion Prevention Systems). Essas ferramentas são mecanismos que são implementados como gateways (in-line) em uma rede de computadores para receber, analisar e encaminhar o tráfego para o seu destino. A análise é feita através da procura por pacotes que contenham assinaturas de ataques aos computadores da rede. Como se trata de uma nova tecnologia é necessário determinar métricas para avaliar os IPS que estão surgindo no mercado. Da mesma forma como acontece com os IDS’s (Intrusion Detection Systems), não é uma tarefa fácil determinar métricas concretas para avaliar os IPS.Eje: I - Workshop de Ingeniería de Software y Base de DatosRed de Universidades con Carreras en Informática (RedUNCI

Metodologia para validar IPS’s de código-fonte aberto

O presente trabalho tem por objetivo descrever uma metodologia para realizar testes com ferramentas IPS (Intrusion Prevention Systems). Essas ferramentas são mecanismos que são implementados como gateways (in-line) em uma rede de computadores para receber, analisar e encaminhar o tráfego para o seu destino. A análise é feita através da procura por pacotes que contenham assinaturas de ataques aos computadores da rede. Como se trata de uma nova tecnologia é necessário determinar métricas para avaliar os IPS que estão surgindo no mercado. Da mesma forma como acontece com os IDS’s (Intrusion Detection Systems), não é uma tarefa fácil determinar métricas concretas para avaliar os IPS.Eje: I - Workshop de Ingeniería de Software y Base de DatosRed de Universidades con Carreras en Informática (RedUNCI

Gonococcal Acute Septic Arthritis in Immunocompetent Patients

The objective of this study is to estimate the clinical evolution and the biological values and of three cases suffering from Gonococcal acute septic arthritis (GASA).Our study is based in a thoroughfully screening of 18 patients hospitalized in our service during the period of time of March 2011 – July 2016. Among those 18 cases, 12 of them (66.7%) were diagnosed with Acute Septic Arthritis (ASA) due to Staphylococcus aureus, 3 cases (16.65%) were diagnosed with ASA due to Neisseria gonorrhoeae, and 3 other cases (16.65%) were diagnosed with ASA due to Streptococcus pneumoniae, Escherichia coli and Echinella corrodens. Two sexually active women at the seventh and tenth day of an untreated suppurative cervico-vaginitis and one man at the eighth day of an untreated suppurative urethritis were consulted at the Service of Infectious Diseases of University Hospital Center “Mother Theresa”, because of: severe pains in left wrist, in the left elbow and in the right knee, swollen of those articulation, difficulties in their movements, shivering and a high fever of   38-39.2ºC. Neisseria gonorrhea was insolated in three cases in blood cultures and cervical/urethral samples and they were sensitive towards Cyclines, Cephalosporins and Fluoroquinolones. All three patients were immunocompetent. Keywords: Neisseria gonorrhea, Acute Septic Arthritis, Biological values

S100A12 in Digestive Diseases and Health: A Scoping Review

Calgranulin proteins are an important class of molecules involved in innate immunity. These members of the S100 class of the EF-hand family of calcium-binding proteins have numerous cellular and antimicrobial functions. One protein in particular, S100A12 (also called EN-RAGE or calgranulin C), is highly abundant in neutrophils during acute inflammation and has been implicated in immune regulation. Structure-function analyses reveal that S100A12 has the capacity to bind calcium, zinc, and copper, processes that contribute to nutritional immunity against invading microbial pathogens. S100A12 is a ligand for the receptor for advanced glycation end products (RAGE), toll-like receptor 4 (TLR4), and CD36, which promote cellular and immunological pathways to alter inflammation. We conducted a scoping review of the existing literature to define what is known about the association of S100A12 with digestive disease and health. Results suggest that S100A12 is implicated in gastroenteritis, necrotizing enterocolitis, gastritis, gastric cancer, Crohn’s disease, irritable bowel syndrome, inflammatory bowel disease, and digestive tract cancers. Together, these results reveal S100A12 is an important molecule broadly associated with the pathogenesis of digestive diseases

IL28B Genetic Variation Is Associated with Spontaneous Clearance of Hepatitis C Virus, Treatment Response, Serum IL-28B Levels in Chinese Population

<p><b>Background:</b> The interleukin-28B gene (IL28B) locus has been associated with host resistance to hepatitis C virus (HCV) infection and response to PEG-IFN/RBV treatment in western populations. This study was to determine whether this gene variant is also associated with spontaneous clearance of HCV infection, treatment response and IL-28B protein production in Chinese patients.</p> <p><b>Methods:</b> We genotyped IL28B genetic variations (rs12980275, rs8103142, rs8099917 and rs12979860) by pyrosequencing DNA samples from cohorts consisting of 529 subjects with persistent HCV infection, 196 subjects who cleared the infection, 171 healthy individuals and 235 chronic HCV patients underwent IFN/RBV treatment. The expression of IL-28B were measured by ELISA and RT-PCR.</p> <p><b>Results:</b> We found that the four IL28B variants were in complete linkage disequilibrium (r2 = 0.97–0.98). The rs12979860 CC genotype was strongly associated with spontaneously HCV clearance and successful IFN/RBV treatment compared to the CT/TT. IL-28B levels in persistent HCV patients were significantly lower than subjects who spontaneously resolved HCV and healthy controls and were also associated with high levels of ALT (alanine aminotransferase) and AST (aspartate aminotransferase). IL-28B levels were also significantly lower in individuals carrying T alleles than CC homozygous.</p> <p><b>Conclusions:</b> Thus, the rs12979860-CC variant upstream of IL28B gene is associated with spontaneous clearance of HCV, susceptible to IFN/RBV treatment and increased IL-28B levels in this Chinese population.</p&gt

Educational profile of young soccer players in the State of Rio de Janeiro

O estudo teve como objetivo descrever o perfil escolar de atletas que atuam no Estado do Rio de Janeiro e que se encontram no período da escolarização básica. O estudo teve uma abordagem quantitativa e qualitativa. Foram realizadas entrevistas estruturadas com amostra não probabilística composta por 417 jogadores das categorias de base, inscritos no ano de 2009 na Federação de Futebol do Estado do Rio de Janeiro e 30 entrevistas semiestruturadas. Os resultados apontaram que os atletas permanecem na escola, todavia a troca de turno escolar e o baixo capital cultural podem afetar negativamente a sua trajetória escolar. A profissionalização no futebol torna-se um projeto familiar e talvez incida sobre o foco que o atleta tenha sobre o processo de escolarização. Os dados sugerem que quanto maior os investimentos do atleta na carreira, maior será a probabilidade de secundarizar os investimentos escolares.The study aimed to describe the educational profile of athletes who work in the State of Rio de Janeiro and in the period of basic schooling. The study had a quantitative and qualitative approach. Structured interviews were conducted with non-probability sample consists of 417 players of the base categories, inscribed in the year 2009 in the Soccer Federation of Rio de Janeiro State and 30 semi-structured interviews. The results showed that the athletes remain at the school; however the flight rotation and low cultural capital can negatively affect his career. To become a professional of soccer is a project which involves all athlete’s family, and maybe this is what makes him not prioritize his formal education. Our data suggest that the more the athlete invest in his career, the more the probability of putting school in the background

Pro-asthmatic cytokines regulate unliganded and ligand-dependent glucocorticoid receptor signaling in airway smooth muscle

To elucidate the regulation of glucocorticoid receptor (GR) signaling under pro-asthmatic conditions, cultured human airway smooth muscle (HASM) cells were treated with proinflammatory cytokines or GR ligands alone and in combination, and then examined for induced changes in ligand-dependent and -independent GR activation and downstream signaling events. Ligand stimulation with either cortisone or dexamethsone (DEX) acutely elicited GR translocation to the nucleus and, comparably, ligand-independent stimulation either with the Th2 cytokine, IL-13, or the pleiotropic cytokine combination, IL-1β/TNFα, also acutely evoked GR translocation. The latter response was potentiated by combined exposure of cells to GR ligand and cytokine. Similarly, treatment with either DEX or IL-13 alone induced GR phosphorylation at its serine-211 residue (GRSer211), denoting its activated state, and combined treatment with DEX+IL-13 elicited heightened and sustained GRSer211phosphorylation. Interestingly, the above ligand-independent GR responses to IL-13 alone were not associated with downstream GR binding to its consensus DNA sequence or GR transactivation, whereas both DEX-induced GR:DNA binding and transcriptional activity were significantly heightened in the presence of IL-13, coupled to increased recruitment of the transcriptional co-factor, MED14. The stimulated GR signaling responses to DEX were prevented in IL-13-exposed cells wherein GRSer211 phosphorylation was suppressed either by transfection with specific serine phosphorylation-deficient mutant GRs or treatment with inhibitors of the MAPKs, ERK1/2 and JNK. Collectively, these novel data highlight a heretofore-unidentified homeostatic mechanism in HASM cells that involves pro-asthmatic cytokine-driven, MAPK-mediated, non-ligand-dependent GR activation that confers heightened glucocorticoid ligand-stimulated GR signaling. These findings raise the consideration that perturbations in this homeostatic cytokine-driven GR signaling mechanism may be responsible, at least in part, for the insensirtivity to glucocorticoid therapy that is commonly seen in individuals with severe asthma