Anti-CCL17 (aa 24-94) polyclonal antibody

Several factors support CLL cell survival in the microenvironment. Under different experimental conditions, IL21 can either induce apoptosis or promote CLL cell survival. To investigate mechanisms involved in the effects of IL21, we studied the ability of IL21 to modulate gene and miRNA expressions in CD40-activated CLL cells. IL21 was a major regulator of chemokine production in CLL cells and it modulated the expression of genes involved in cell movement, metabolism, survival and apoptosis. In particular, IL21 down-regulated the expression of the chemokine genes CCL4, CCL3, CCL3L1, CCL17, and CCL2, while it upregulated the Th1-related CXCL9 and CXCL10. In addition, IL21 down-regulated the expression of genes encoding signaling molecules, such as CD40, DDR1 and PIK3CD. IL21 modulated a similar set of genes in CLL and normal B-cells (e.g. chemokine genes), whereas other genes, including MYC, TNF, E2F1, EGR2 and GAS-6, were regulated only in CLL cells. An integrated analysis of the miRNome and gene expression indicated that several miRNAs were under IL21 control and these could, in turn, influence the expression of potential target genes. We focused on hsa-miR-663b predicted to down-regulate several relevant genes. Transfection of hsa-miR-663b or its specific antagonist showed that this miRNA regulated CCL17, DDR1, PIK3CD and CD40 gene expression. Our data indicated that IL21 modulates the expression of genes mediating the crosstalk between CLL cells and their microenvironment and miRNAs may take part in this process.

Background: A subpopulation of patients with chronic hepatitis B virus (HBV) infection coupled with moderate/severe liver necro-inflammation were analyzed. The results show normal/mildly elevated alanine transaminase (ALT) levels. Objective: The goal of this study was to investigate the role of serum chemokine profiles as a possible biomarker of hepatic necro-inflammation in patients with HBV infection and normal/mildly elevated ALT levels. Method: A total of 122 previously untreated patients with chronic HBV infection and normal/mildly elevated ALT levels underwent liver biopsy and histological grading of liver necro-inflammation (G0-G4). Levels of 13 serum chemokines was measured by flow cytometry. Expression of selected increased chemokines was further verified by enzyme-linked immunosorbent assay (ELISA). Results: Expression of (C-C motif) ligand 2 (CCL2), CCL11, CCL17, and chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL5, and CXCL11 were upregulated in the patients with moderate or severe liver necro-inflammation. Serum levels of CCL2 and CCL17 were significantly elevated in patients with chronic HBV infection and significant liver necro-inflammation, compared to those with mild liver necro-inflammation. CCL2 and CCL17 were the risk factors for significant liver necro-inflammation (P=0.012 and P=0.014, respectively). The area under the receiver operating characteristics curve (AUROC) for predicting significant necro-inflammation of combined CCL2 and CCL17 were 0.83, with 78.57% and 71.43% sensitivity and specificity, respectively. Conclusion: High levels of CCL2 and CCL17 are correlated with hepatic necro-inflammation, and these chemokines may be useful as serum biomarkers for liver necro-inflammation in patients with chronic HBV infection and normal/mildly elevated ALT.