The liver contains two distinct populations of macrophages, monocyte-derived macrophages (MDMs), which primarily reside proximal to the Glisson’s capsule and Kupffer cells, which reside within the sinusoids. Kupffer cells infiltrate the liver during embryogenesis and are replenished from local proliferation of mature Kupffer cells. By contrast MDMs arise from hematopoietic stem cells in the bone marrow and are replenishedfrom circulating monocytes. Studies have revealed that these two hepatic macrophage populations possess distinct transcriptomic profiles, suggesting that they may be functionally distinct. In the present study, we tested the hypothesis that MDMs and Kupffer cells are differentially sensitive to bacterial lipopolysaccharide (LPS). MDMs and Kupffer cells were purified to greater than 90% from the livers of mice by using magnetic beads labeled with Cx3cr1 antibody for MDMs and F4/80 antibody for Kupffer cells. Basal levels of tumor necrosis factor-α (TNF-α) mRNA were higher in MDMs when compared to Kupffer cells. After treatment with LPS, mRNA levels of TNF-α, Cxcll, and Cxcl2 were increased to a greater extent in MDMs when compared to Kupffer cells. To confirm these findings, Kupffer cells and MDMs were isolated from mice in which bone marrow transplantation was used to selectively tag cells arising from hematopoietic stem cells in adult mice. Similar to above, treatment of MDMs with LPS increased TNF-α, Cxcll, and Cxcl2 to a greater extent when compared to Kupffer cells. Collectively, these results indicate that MDMs exhibit a greater pro-inflammatory phenotype in the liver when exposed to LPS.
Background: Identifying active small bowel Crohn's Disease (CD) is often challenging due to various reasons.The location of Crohn's disease and often the disease process itself make direct visualization difficult.Fecal calprotectin (FCP) is a well-established marker of mucosal inflammation.Several studies have confirmed FCP's utility in colonic inflammation; however, the diagnostic accuracy in active small bowel inflammation had yet to be established.The aim of the present study is to update the previous meta-analysis of FCP and its diagnostic accuracy in detecting active small bowel Crohn's disease.Methods: Study Selection Criteria: A comprehensive search was performed using PubMed/OVID studies.Studies from 2010 until 2018 addressing patients with suspected or known CD and evaluated with noninvasive testing with FCP and confirming disease with video capsule endoscopy or imaging were included.Studies in which a 2 × 2 table with true positives, false negatives, false positives and true negative values could be constructed were included.Statistical Method: Meta-analysis for the diagnostic accuracy of fecal calprotectin in diagnosing active small bowel CD was performed by calculating pooled estimates of sensitivity, specificity, likelihood rations, and diagnostic odds ratios.Pooling was conducted by both fixed and random effects models.Results: Data was extracted from 17 studies which met the inclusion criteria.In CD patients, pooled sensitivity of fecal calprotectin was 76.50% (95% CI: 73.00 -79.00) in diagnosing small bowel Crohn's disease.Fecal calprotectin had a pooled specificity of 71.10% (95% CI: 68.00 -73.00) for detecting active small bowel Crohn's disease.The diagnostic odds ratio, of having active small bowel disease with elevated FCP was .The positive likelihood ratio of FCP was 3.09 (95% CI: 2.16 -4.41), and the negative likelihood ratio was 0.30 (95% CI: 0.21 -0.43).Conclusion: Fecal calprotectin has moderate diagnostic accuracy for detecting active small bowel CD.Our results suggest a fecal calprotectin of at least 50 µg/g has moderate sensitivity and specificity in detecting active small bowel disease.
We sought to determine if the baseline hepatic levels of miR-122, miR-29b, Claudin, Occludin, Protein Kinase R (PKR) or PKR activator (PRKRA) were correlated with HCV RNA or stage of fibrosis in patients with chronic hepatitis C (CHC). A total of 25 CHC patients (genotype 1) who were treatment naive at the time of sample collection enrolled in this study. By multivariate analysis, CLDN RNA was found as the single independent factor positively correlated with HCV RNA levels (p=0.003), while hepatic miR-29b levels was found as the single independent factor for predicting advanced stage of fibrosis (p=0.028). Conclusion: Our results highlight miR-29b and CLDN as novel predictors of advanced stage of liver fibrosis and baseline HCV RNA in CHC.
