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Coexpression and interaction of CXCL10 and CD26 in mesenchymal cells by synergising inflammatory cytokines: CXCL8 and CXCL10 are discriminative markers for autoimmune arthropathies.

ABSTRACT: Leukocyte infiltration during acute and chronic inflammation is regulated by exogenous and endogenous factors, including cytokines, chemokines and proteases. Stimulation of fibroblasts and human microvascular endothelial cells with the inflammatory cytokines interleukin-1beta (IL-1beta) or tumour necrosis factor alpha (TNF-alpha) combined with either interferon-alpha (IFN-alpha), IFN-beta or IFN-gamma resulted in a synergistic induction of the CXC chemokine CXCL10, but not of the neutrophil chemoattractant CXCL8. In contrast, simultaneous stimulation with different IFN types did not result in a synergistic CXCL10 protein induction. Purification of natural CXCL10 from the conditioned medium of fibroblasts led to the isolation of CD26/dipeptidyl peptidase IV-processed CXCL10 missing two NH2-terminal residues. In contrast to intact CXCL10, NH2-terminally truncated CXCL10(3-77) did not induce extracellular signal-regulated kinase 1/2 or Akt/protein kinase B phosphorylation in CXC chemokine receptor 3-transfected cells. Together with the expression of CXCL10, the expression of membrane-bound CD26/dipeptidyl peptidase IV was also upregulated in fibroblasts by IFN-gamma, by IFN-gamma plus IL-1beta or by IFN-gamma plus TNF-alpha. This provides a negative feedback for CXCL10-dependent chemotaxis of activated T cells and natural killer cells. Since TNF-alpha and IL-1beta are implicated in arthritis, synovial concentrations of CXCL8 and CXCL10 were compared in patients suffering from crystal arthritis, ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis. All three groups of autoimmune arthritis patients (ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis) had significantly increased synovial CXCL10 levels compared with crystal arthritis patients. In contrast, compared with crystal arthritis, only rheumatoid arthritis patients, and not ankylosing spondylitis or psoriatic arthritis patients, had significantly higher synovial CXCL8 concentrations. Synovial concentrations of the neutrophil chemoattractant CXCL8 may therefore be useful to discriminate between autoimmune arthritis types.

SUBMITTER: Proost P

PROVIDER: S-EPMC1779382 | biostudies-other | 2006

REPOSITORIES: biostudies-other

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Project description:BackgroundChronic hepatitis B (CHB) remains a significant global health problem, leading to recurrent inflammation and liver-damaging diseases such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Currently, although diagnostic markers for CHB are well established, the indicators for predicting liver injury caused by hepatitis B virus (HBV) infection still need to be further explored. Thus, the identification of credible infectious indicators is urgently needed to facilitate timely clinical intervention and avoid the progression of disease malignancy.MethodsThe Gene Expression Omnibus (GEO) database GSE83148 data set was used to explore the hub genes for HBV infection. The quantitative real-time polymerase chain reaction (qPCR) was used to identify the impact of HBV infection on the expression of hub gene at the cell level. At the same time, serum samples and clinical information were collected from healthy, HBV-free and CHB patients. The enzyme-linked immunosorbent assay (ELISA) was used to verify the results of cell experiments and Pearson correlation analysis was used to clarify hub genes correlation with HBV infection indicators and liver injury-related indicators. Finally, the Gene Expression Profiling Interactive Analysis (GEPIA) database was used to analyze the differences in the expression of hub gene in liver injury diseases.ResultsChemokine (C-X-C motif) ligand (CXCL)8, CXCL9, CXCL10, and CXCL11 were identified as hub genes in HBV infection. After HBV infection, the expression of the four chemokines was significantly increased and the concentrations secreted into serum were also increased. Moreover, the four chemokines were significantly correlated with HBV infection-related indicators and liver injury-related indicators, which were positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatitis B e antigen (HBeAg), and negatively correlated with AST/ALT ratio and hepatitis B core antibody (HBcAb). In addition, the expression of CXCL9, CXCL10, and CXCL11 in HCC tissues was significantly higher than in normal tissues.ConclusionUsing a combination of bioinformatics, cell experiments, and clinical correlation analysis, this study showed that CXCL8, CXCL9, CXCL10, and CXCL11 can be used as serum biomarkers to forecast liver injury caused by HBV infection.

Project description:BackgroundHuman African trypanosomiasis (HAT), also known as sleeping sickness, is a parasitic tropical disease. It progresses from the first, haemolymphatic stage to a neurological second stage due to invasion of parasites into the central nervous system (CNS). As treatment depends on the stage of disease, there is a critical need for tools that efficiently discriminate the two stages of HAT. We hypothesized that markers of brain damage discovered by proteomic strategies and inflammation-related proteins could individually or in combination indicate the CNS invasion by the parasite.MethodsCerebrospinal fluid (CSF) originated from parasitologically confirmed Trypanosoma brucei gambiense patients. Patients were staged on the basis of CSF white blood cell (WBC) count and presence of parasites in CSF. One hundred samples were analysed: 21 from stage 1 (no trypanosomes in CSF and <or=5 WBC/microL) and 79 from stage 2 (trypanosomes in CSF and/or >5 WBC/microL) patients. The concentration of H-FABP, GSTP-1 and S100beta in CSF was measured by ELISA. The levels of thirteen inflammation-related proteins (IL-1ra, IL-1beta, IL-6, IL-9, IL-10, G-CSF, VEGF, IFN-gamma, TNF-alpha, CCL2, CCL4, CXCL8 and CXCL10) were determined by bead suspension arrays.ResultsCXCL10 most accurately distinguished stage 1 and stage 2 patients, with a sensitivity of 84% and specificity of 100%. Rule Induction Like (RIL) analysis defined a panel characterized by CXCL10, CXCL8 and H-FABP that improved the detection of stage 2 patients to 97% sensitivity and 100% specificity.ConclusionThis study highlights the value of CXCL10 as a single biomarker for staging T. b. gambiense-infected HAT patients. Further combination of CXCL10 with H-FABP and CXCL8 results in a panel that efficiently rules in stage 2 HAT patients. As these molecules could potentially be markers of other CNS infections and disorders, these results should be validated in a larger multi-centric cohort including other inflammatory diseases such as cerebral malaria and active tuberculosis.

Project description:Objectives: To investigate the changes of dry eye-related clinical manifestations, ocular surface parameters, and tear inflammatory cytokines after upper blepharoplasty. Methods: Forty eyes of 20 who underwent upper blepharoplasty were divided into either the group with or the group without preexisting dry eye before upper blepharoplasty. Ocular Surface Disease Index (OSDI), Schirmer I test, tear meniscus height, lipid layer thickness, non-invasive tear break-up time (NIKBUT), fluorescein tear film break-up time (FBUT), corneal fluorescein staining, meibum expression, lid margin changes, and tear inflammatory cytokines were assessed preoperatively and at 1, 3, and 6 months postoperatively. Correlations between inflammatory cytokines and dry eye-related parameters were determined. Results: The OSDI scores increased significantly at 1 month (p = 0.040) and subsequently decreased to the preoperative levels at 6 months postoperatively in subjects with dry eye. First (f)-NIKBUT and FBUT were significantly shortened at 1, 3, and 6 months postoperatively in subjects with dry eye (f-NIKBUT: p <0.001, p = 0.010, p = 0.042; FBUT: p = 0.002, p = 0.005, p = 0.037, respectively), but were only shortened at 1 month (p = 0.028, p = 0.005) and returned to baseline levels at 6 months postoperatively in subjects without preexisting dry eye. A significant increasing trend of interleukin (IL)-6 was found in both dry eye and subjects without preexisting dry eye (p = 0.016, p = 0.008), while IL-8 and tumor necrosis factor alpha (TNF-α) were only found to be increased in subjects with dry eye postoperatively (p = 0.031, p = 0.031). The levels of IL-8 and TNF-α were positively correlated with OSDI scores (p = 0.046, p = 0.043, respectively) and negatively correlated with f-NIKBUT and FBUT (p = 0.026, p = 0.006, respectively). Conclusions: Upper blepharoplasty might increase the release of tear inflammatory cytokines and tear film instability that contribute to the development of postoperative dry eye in the early postoperative period and the changes most relieved in 6 months. Preexisting dry eye is a higher risk factor for worse and persistent ocular surface damage after upper blepharoplasty.

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Coexpression and interaction of CXCL10 and CD26 in mesenchymal cells by synergising inflammatory cytokines: CXCL8 and CXCL10 are discriminative markers for autoimmune arthropathies.

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