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1.
Pediatr Nephrol ; 32(8): 1391-1400, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28229280

RESUMO

BACKGROUND: The aim of this cross-sectional study was to investigate inflammatory biomarkers in urine samples of 24 fetuses with posterior urethral valve (PUV) collected at 22 ± 4 weeks of gestation and to compare the findings with measurements in urine samples of 22 male healthy preterm neonates at 23 ± 4 weeks (control group). METHODS: Inflammatory biomarkers in urine were measured using a cytometric bead array [interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ, soluable tumor necrosis factor receptor (TNFR) 1, sTNFR2, monocyte chemoattractant protein-1/chemokine ligand 2 (MCP-1/CCL2), eotaxin/CCL11 and interferon gamma-induced protein/10/C-X-C motif chemokine 10 (IP-10/CXCL10)] and ELISA assays [TNF, IL-8/CXCL8 and transforming growth factor-beta (TGF-ß)]. The Mann-Whitney test was used to compare medians. Markers of glomerular (creatinine) and tubular [beta 2 (ß2)-microglobulin, uromodulin, osmolality] functions were correlated with inflammatory biomarkers (Spearman test). RESULTS: An intense inflammatory profile was identified, with significantly increased concentrations of urinary IL-2, IL-4, IL-6, TNF, sTNFRI, sTNFRII, IFN-γ, MCP-1/CCL2, eotaxin/CCL11 and IL-8/CXCL8 in the PUV group compared to the controls. The same was observed for the anti-inflammatory cytokine IL-10 and for the fibrogenic mediator TGF-ß. In the correlation analysis, ß2-microglobulin positively correlated with the presence of MCP-1/CCL2, sTNFRI and eotaxin/CCL11 and negatively correlated with the presence of creatinine. CONCLUSIONS: This study shows that inflammatory molecules are already increased in fetuses with PUV at the mean gestational age of 22 weeks, suggesting a physiopathological role for inflammation just after the embryological formation of the urethral membrane.


Assuntos
Citocinas/urina , Feto/anormalidades , Lactente Extremamente Prematuro/urina , Uretra/anormalidades , Doenças Uretrais/urina , Biomarcadores/urina , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Testes de Função Renal , Masculino , Gravidez , Ultrassonografia , Uretra/diagnóstico por imagem , Doenças Uretrais/diagnóstico por imagem
2.
J Immunol ; 185(9): 5569-76, 2010 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-20935211

RESUMO

Activation of the renin-angiotensin (Ang) system induces inflammation via interaction between Ang II and type 1 receptor on leukocytes. The relevance of the new arm of the renin-Ang system, namely Ang-converting enzyme-2/Ang-(1-7)/Mas receptor, for inflammatory responses is not known and was investigated in this study. For this purpose, two experimental models were used: Ag-induced arthritis (AIA) in mice and adjuvant-induced arthritis (AdIA) in rats. Male C57BL/6 wild-type or Mas(-/-) mice were subjected to AIA and treated with Ang-(1-7), the Mas agonist AVE 0991, or vehicle. AdIA was performed in female rats that were given AVE 0991 or vehicle. In wild-type mice, Mas protein is expressed in arthritic joints. Administration of AVE 0991 or Ang-(1-7) decreased AIA-induced neutrophil accumulation, hypernociception, and production of TNF-α, IL-1ß, and CXCL1. Histopathological analysis showed significant reduction of inflammation. Mechanistically, AVE 0991 reduced leukocyte rolling and adhesion, even when given after Ag challenge. Mas(-/-) mice subjected to AIA developed slightly more pronounced inflammation, as observed by greater neutrophil accumulation and cytokine release. Administration of AVE 0991 was without effect in Mas(-/-) mice subjected to AIA. In rats, administration of AVE 0991 decreased edema, neutrophil accumulation, histopathological score, and production of IL-1ß and CXCL1 induced by AdIA. Therefore, activation of Mas receptors decreases neutrophil influx and cytokine production and causes significant amelioration of arthritis in experimental models of arthritis in rats and mice. This approach might represent a novel therapeutic opportunity for arthritis.


Assuntos
Anti-Inflamatórios/farmacologia , Artrite Experimental/imunologia , Imidazóis/farmacologia , Proteínas Proto-Oncogênicas/agonistas , Receptores Acoplados a Proteínas G/agonistas , Animais , Artrite Experimental/patologia , Western Blotting , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/imunologia , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/imunologia
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