Chronic mineral oil administration increased hepatic inflammation in wild type mice compared to lipocalin 2 null mice
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ABSTRACT: Concerning the roles of LCN2 in chronic inflammation and fibrosis, we investigated chronic liver inflammation and fibrosis using repeated carbon tetrachloride (CCl4) in mineral oil injection. We found that mice treated with the mineral oil vehicle alone also showed liver inflammation and more severe in wild-type mice compared to lipocalin 2 null mice.
Project description:To investigate the differences in microRNA expression profiles between fibrotic and normal livers, we performed microRNA microarrays for total RNA extracts isolated from mouse livers treated with carbontetrachloride (CCl4) or corn-oil for 10 weeks (n=3/group). MicroRNAs were considered to have significant differences in expression level when the expression difference showed more than two-fold change between the experimental and control groups at p<0.05. We found that 12 miRNAs were differentially expressed in CCl4-induced fibrotic liver. To induce chronic liver fibrosis, seven-week-old mice received 0.6 ml/kg body weight of carbon-tetrachloride (CCl4) dissolved in corn-oil by intraperitoneal (i.p.) injection, twice a week for 10 weeks (n=3). As a control, same number of mice was injected with equal volume of corn-oil for 10 weeks.
Project description:Anaemia is a frequent complication of chronic infectious diseases but the exact mechanisms by which it develops remain to be clarified. In the present work, we used a mouse model of mycobacterial infection to study molecular alterations of iron metabolism. We show that four weeks after infection with Mycobacterium avium BALB/c mice exhibit a moderate anaemia, which cannot be explained by elevated hepatic hepcidin mRNA expression. Instead, the mice respond with increased mRNA expression of ferroportin (Slc40a1), ceruloplasmin (Cp), hemopexin (Hpx), heme-oxygenase-1 (Hmox1) and lipocalin-2 (Lcn2). Both the anemia and the mRNA expression changes of iron-related genes are largely absent in C.D2 mice which bear a functional allele of the Nramp1 gene. These data suggest that anaemia due to a chronic infection with M. avium develops independently of elevated hepcidin expression and possibly involves ferroportin and/or lipocalin-2. A pool of five mice total RNAs for each condition was used in the experiments. Each two channel chip experiment was done in duplicates with swapped dyes.
Project description:Anaemia is a frequent complication of chronic infectious diseases but the exact mechanisms by which it develops remain to be clarified. In the present work, we used a mouse model of mycobacterial infection to study molecular alterations of iron metabolism. We show that four weeks after infection with Mycobacterium avium BALB/c mice exhibit a moderate anaemia, which cannot be explained by elevated hepatic hepcidin mRNA expression. Instead, the mice respond with increased mRNA expression of ferroportin (Slc40a1), ceruloplasmin (Cp), hemopexin (Hpx), heme-oxygenase-1 (Hmox1) and lipocalin-2 (Lcn2). Both the anemia and the mRNA expression changes of iron-related genes are largely absent in C.D2 mice which bear a functional allele of the Nramp1 gene. These data suggest that anaemia due to a chronic infection with M. avium develops independently of elevated hepcidin expression and possibly involves ferroportin and/or lipocalin-2.
Project description:The Forkhead Box f1 (Foxf1) transcriptional factor (previously known as HFH-8 or Freac-1) is expressed in endothelial and smooth muscle cells in the embryonic and adult lung. To assess effects of Foxf1 during lung injury, we used CCl4 injury model. Foxf1+/- mice developed severe airway obstruction and bronchial edema, associated with increased numbers of pulmonary mast cells and increased mast cell degranulation following injury. Pulmonary inflammation in Foxf1+/- mice was associated with diminished expression of Foxf1, increased mast cell tryptase and increased expression of CXCL12, the latter being essential for mast cell migration and chemotaxis. Foxf1 haploinsufficiency caused pulmonary mastocytosis and enhanced pulmonary inflammation following chemically-induced lung injury, indicating an important role for Foxf1 in the pathogenesis of pulmonary inflammatory responses. Keywords: Influence of genetic modification on the pulmonary inflamation Foxf1+/- mice in which the Foxf1 allele was disrupted by an in-frame insertion of a nuclear localizing -galactosidase (-Gal) gene were bred for ten generations into the Black Swiss mouse genetic background. Carbon tetrachloride (CCl4; Sigma, St Louis, MO) was dissolved in mineral oil at a 1:20 ratio v/v and a single intraperitoneal (i.p.) injection of CCl4 (0.5 l of CCl4/ 1g of body weight) was administered to male Foxf1+/- mice or their wild type (WT) littermates as described.