CC Chemokine Receptor 2 Promotes Recruitment of Myeloid Cells Associated with Insulin Resistance in Non-Alcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a common disease, closely associated with obesity and insulin resistance. We investigated the presence of a subset of myeloid cells associated with metabolic disturbance in the liver of patients with NAFLD and a murine model of obesity-induced liver disease. Gene and protein expression in liver and serum was investigated with RT-PCR or ELISA and correlated to clinical disease. Liver-infiltrating immune cells were isolated from normal or diseased human liver for flow cytometric analysis. In animal experiments, mice were fed a high-fat diet (60% of calories from fat) for 16 wk, or high-fat diet with 30% fructose for 32 wk to induce steatohepatitis and fibrosis. A small molecule inhibitor of CC chemokine receptor 2 (CCR2), CCX872, was administered to some mice. A subset of CD11c+CD206+ immune cells was enriched in human liver tissue, and greater infiltration was observed in NAFLD. The presence of CD11c+CD206+ myeloid cells correlated with systemic insulin resistance. CD11c+CD206+ cells expressed high levels of CCR2, and liver CC chemokine ligand 2 (CCL2) expression was increased in nonalcoholic steatohepatitis and correlated with disease activity. In mice, CCR2 inhibition reduced infiltration of liver CD11b+CD11c+F4/80+ monocytes, which are functional homologs of human CD11c+CD206+ cells, and improved liver injury and glycemic control. A role for CCR2/CCL2 in human NAFLD has long been postulated. These data confirm a role for this chemokine/receptor axis, through mediating adipose and hepatic infiltration of myeloid cells. Inhibition of CCR2 improved hepatic inflammation and fibrosis in murine models of NAFLD. These data confirm the rationale for targeting CCR2 to treat NAFLD. NEW &amp; NOTEWORTHY These data show for the first time that CD11c+CD206+ myeloid cells, previously associated with human adipose tissue inflammation, infiltrate into liver tissue in nonalcoholic fatty liver disease. These cells express CCR2. Inhibition of CCR2 in mice inhibits hepatic inflammation caused by a murine homolog of these myeloid cells and improves experimental liver disease. </jats:p

Effects of carbofuran and metsulfuron-methyl on the benthic macroinvertebrate community in flooded ricefields Efeito do carbofurano e metsulfuron-methyl sobre a comunidade de macroinvertebrados bentônicos de lavoura de arroz irrigado

AIM: This study evaluated the effect of the insecticide carbofuran and the herbicide metsulfuron-methyl on the abundance and diversity of benthic macroinvertebrates in a paddy ricefield. METHODS: To achieve this goal, two pesticide treatments [the insecticide carbofuran (IC) and the herbicide metsulfuron-methyl (HM)] and a control (Co) treatment with no added pesticide were established in an experimental area of the Plant Science Department of the Federal University of Santa Maria. Soil samples were collected in triplicate from each treatment 30 days before and 1, 10, and 51 days after the pesticide application, for macrofauna identification. RESULTS: Among the 21 taxa identified, Trichoceridae was present only in Co, Hydroptilidae was recorded only in IC, and Corixidae in HM. In Co, the most abundant group was Annelida, while in IC and HM Diptera (Chironomidae) was dominant. Significant differences were observed between Co and IC, in the density of Odontoceridae (Control>IC) and Hydrophilidae (Control<IC), and between Co and HM in the density of Odontoceridae (Control>HM) and Hirudinea (Control<HM). CONCLUSION: In spite of the possible negative effects of the pesticides on the benthic community, the assemblages recovered rapidly.<br>OBJETIVO: O objetivo desse estudo foi avaliar o efeito do inseticida carbofurano e do herbicida metsulfuron-methyl na abundância e diversidade de macroinvertebrados bentônicos em campo de arroz irrigado. MÉTODOS: Para isto, dois tratamentos com agrotóxicos [o inseticida carbofurano (IC) e o herbicida metsulfuron-methyl (HM)] e um controle (Co), tratamento sem pesticida, foram aplicados em uma área experimental no Departamento de Fitotecnia da Universidade Federal de Santa Maria. Amostras de solo foram coletadas em triplicatas em cada tratamento 30 dias antes (DBA) e 1, 10 e 51 dias após a aplicação dos pesticidas, posteriormente a macrofauna foi identificada. RESULTADOS: Vinte e um (21) taxa foram identificados, entre esses Trichoceridae esteve presente apenas em Co, enquanto que Hydroptilidae foi coletado apenas em IC, e Corixidae em HM. Em Co e IC, o grupo mais abundante foi Annelida, e em HM foi Diptera (Chironomidae) que prevaleceu. Diferenças significativas foram observadas entre Co e IC, na densidade de Odontoceridae (Co>IC) e Hydrophilidae (Co<IC), e entre Co e HM na densidade de Odontoceridae (Co>HM) e Hirudinea (Co<HM). CONCLUSÃO: Entretanto, apesar dos possíveis efeitos negativos dos pesticidas sobre a comunidade bentônica verificados nos primeiros dias após a aplicação, verificou-se que de forma geral a comunidade recuperou-se rapidamente