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1.
Nutr Cancer ; 73(4): 642-651, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32406264

RESUMO

There is a strong correlation between obesity and cancer. Here, we investigated the influence of IL-6 and gut microbiota of obese mice in melanoma development. We first evaluated B16F10 melanoma growth in preclinical models for obesity: mice deficient for leptin (ob/ob) or adiponectin (AdpKO) and in wild-type mice (WT, C57BL/6J) fed a high-fat diet (HFD; 60% kcal from fat) for 12 weeks. The survival rates of ob/ob and HFD-fed mice were lower than those of their respective controls. AdpKO mice also died earlier than WT control mice. We then verified the involvement of IL-6 signaling in obese mice that were inoculated with melanoma cells. Both ob/ob and AdpKO mice had higher circulating IL-6 levels than wild-type mice. Melanoma tumor volumes in IL-6 KO mice fed an HFD were reduced compared to those of WT mice subjected to the same diet. Also evaluated the effect of microbiota in tumor development. Cohousing and fecal matter transfer experiments revealed that microbiota from ob/ob mice can stimulate tumor development in lean WT mice. Taken together, our data show that in some conditions IL-6 and the gut microbiota are key mediators that link obesity and melanoma.


Assuntos
Microbioma Gastrointestinal , Melanoma , Animais , Dieta Hiperlipídica/efeitos adversos , Interleucina-6 , Leptina , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos
2.
Int Immunopharmacol ; 64: 151-161, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30176533

RESUMO

Acute kidney injury (AKI) and chronic kidney disease (CKD) are major concerns in worldwide public health, and their pathophysiology involves immune cells activation, being macrophages one of the main players of both processes. It is suggested that metabolic pathways could contribute to macrophage modulation and phosphatidylinositol­3 kinase (PI3K) pathway was shown to be activated in kidneys subjected to ischemia and reperfusion as well as unilateral ureteral obstruction (UUO). Although PI3K inhibition is mostly associated with anti-inflammatory response, its use in kidney injuries has been shown controversial results, which indicates the need for further studies. Our aim was to unveil the role of PI3Kγ in macrophage polarization and in kidney diseases development. We analyzed bone-marrow macrophages polarization from wild-type (WT) and PI3Kγ knockout (PI3K KO) animals. We observed increased expression of M1 (CD86, CCR7, iNOS, TNF, CXCL9, CXCL10, IL-12 and IL-23) and decreased of M2 (CD206, Arg-1, FIZZ1 and YM1) markers in the lack of PI3Kγ. And this modulation was accompanied by higher levels of inflammatory cytokines in PI3K KO M1 cells. PI3K KO mice had increased M1 in steady state kidneys, and no protection was observed in these mice after acute and chronic kidney insults. On the contrary, they presented higher levels of protein-to-creatinine ratio and Kim-1 expression and increased tubular injury. In conclusion, our findings demonstrated that the lack of PI3Kγ favors M1 macrophages polarization providing an inflammatory-prone environment, which does not prevent kidney diseases progression.


Assuntos
Injúria Renal Aguda/prevenção & controle , Polaridade Celular , Classe Ib de Fosfatidilinositol 3-Quinase/fisiologia , Macrófagos/fisiologia , Insuficiência Renal Crônica/prevenção & controle , Animais , Progressão da Doença , Inflamação/etiologia , Interleucina-12/biossíntese , Camundongos , Camundongos Endogâmicos C57BL , Obstrução Ureteral/complicações
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