Background and aimsGlycoprotein nonmetastatic melanoma B (Gpnmb), a transmembrane glycoprotein that is expressed in macrophages, negatively regulates inflammation. We have reported that Gpnmb is strongly expressed in the livers of rats fed a choline-deficient, L-amino acid-defined (CDAA) diet. However, the role of macrophage-expressed Gpnmb in liver injury is still unknown. This study aimed to clarify the characteristics of infiltrating macrophages that express Gpnmb, and the involvement of Gpnmb in the repair process in response to liver injury.MethodsC57BL/6J, DBA/2J [DBA] and DBA/2J-Gpnmb+ [DBA-g+] mice were treated with a single intraperitoneal injection of carbon tetrachloride (CCl4) at a dose of 1.0 mL/kg body weight. Mice were sacrificed at predetermined time points, followed by measurement of serum alanine aminotransferase (ALT) levels and histological examination. Expression of Gpnmb, pro-/anti-inflammatory cytokines, and profibrotic/antifibrotic factors were examined by quantitative RT-PCR and/or Western blotting. Immunohistochemistry, fluorescent immunostaining and flow cytometry were used to determine the expression of Gpnmb, CD68, CD11b and α-SMA, phagocytic activity, and the presence of apoptotic bodies. We used quantitative RT-PCR and ELISA to examine TGF-β and MMP-13 expression and the concentrations and supernatants of isolated infiltrating hepatic macrophages transfected with siGpnmb.ResultsIn C57BL/6J mice, serum ALT levels increased at two days after CCl4 injection and decreased at four days. Gpnmb expression in the liver was stimulated four days after CCl4 injection. Histological examination and flow cytometry showed that Gpnmb-positive cells were almost positive for CD68-positive macrophages, contained engulfed apoptotic bodies and exhibited enhanced phagocytic activity. Isolated infiltrating hepatic macrophages transfected with siGpnmb showed high MMP-13 secretion. There was no significant difference in the magnitude of CCl4-induced liver injury between DBA-g+ and DBA mice. However, hepatic MMP-13 expression, as well as α-SMA expression and collagen production, increased significantly in DBA-g+ compared with DBA mice.ConclusionsGpnmb-positive macrophages infiltrate the liver during the recovery phase of CCl4–induced acute liver injury and contribute to the balance between fibrosis and fibrolysis in the repair process following acute liver injury.
Excessive fructose intake is a risk factor for gut symptoms in patients with inflammatory bowel disease, however, its effect on the intestinal tract has not been evaluated previously. The present study investigated the impact of a high-fructose diet (HFd) on intestinal barrier function in mice with experimental colitis. c57/BL6 mice were provided with either a HFd or control diet and either plain drinking water or water containing 1% dextran sulfate sodium (dSS) for 2 weeks. The disease activity index (dAI), pathological scores and expression of inflammatory cytokines were compared among the groups, and the proportions of fecal bacteria in the colon were analyzed. The body weight and colon length were significantly decreased, and the DAI and pathological scores were significantly increased in the DSS/HFD-treated mice compared with the non-dSS-treated and control diet mice. Regarding the expression of inflammatory cytokines, the levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α were significantly increased, and the expression of the tight junction protein occludin was significantly decreased in the dSS/HFd-treated mice. The total bacterial count was increased in the HFd mice. Taken together, these results indicate that an HFd resulted in the deterioration of intestinal barrier function and increased susceptibility to dSS-induced colitis.
dysbiosis of the enteric microbiota causes gastrointestinal diseases, including colitis. The present study investigated the beneficial effect of Lactobacillus plantarum 06cc2 in experimental colitis in mice. an experimental colitis model in c57Bl6 mice was induced using dextran sulfate sodium. Mice were orally administered 06cc2 (06cc2 group) or PBS only (control group) by gavage. The disease activity index (dai), histological grading, and colon tissue and colonic lamina propria mononuclear cells (lPMcs) were examined macroscopically and histopathologically, and the expression levels of inflammation-associated cytokines (il-6, il-12, TnF-α and il-10) in these samples were determined. compared with the control group, the 06cc2 group exhibited a significantly lower dai (1.5±0.8 vs. 0.2±0.3, respectively; P<0.05) and pathology score (6.3±1.5 vs. 3.8±1.3, respectively; P<0.05). il-10 expression in colonic lPMcs was higher in the 06cc2 group than in the control group, although there was no significant difference in IFN-γ, il-6 or il-12 expression in colonic lPMcs between the two groups. in addition, 06cc2 stimulated the production of il-10 from cd11b-positive cells and cd11c-positive cells in the colon. The 06cc2 strain induced il-10 production in the colon and attenuated colon inflammation.
Background/Aim: Fecal markers have recently been found to provide convenient and noninvasive assessment of intestinal inflammation in inflammatory bowel disease (IBD). In this study, we examined the clinical significance of fecal human neutrophil peptides (F-HNP) in the evaluation of IBD disease activity. Methods: This study enrolled 70 patients with IBD, consisting of 45 patients with ulcerative colitis (UC), 25 patients with Crohn's disease (CD), and 11 non-IBD controls. Stools samples were evaluated for the association between F-HNP concentration and disease and endoscopic activity in each group and the correlation between F-HNP and fecal calprotectin (F-CP) concentrations. Results: Median F-HNP levels were as follows: UC: 25.6 ng/ml; CD: 20.1 ng/ml; and non-IBD controls: 4.9 ng/ml. F-HNP levels were significantly higher in each IBD group, especially in the UC group, than in the control group. In the UC group, both F-HNP and F-CP levels were significantly higher during active disease compared to the remission phase. Both markers were significantly correlated with the Mayo endoscopic score, although the correlation was stronger for F-HNP than for F-CP (r = 0.66 vs. r = 0.54). Conclusion: F-HNP is a noninvasive marker that is useful for evaluating UC endoscopic activity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.