CCL24 regulates biliary inflammation and fibrosis in primary sclerosing cholangitis.

ˆCCL24 is a pro-fibrotic, pro-inflammatory chemokine expressed in several chronic fibrotic diseases. In the liver, CCL24 plays a role in fibrosis and inflammation, and blocking CCL24 led to reduced liver injury in experimental models. We studied the role of CCL24 in primary sclerosing cholangitis (PSC) and evaluated the potential therapeutic effect of blocking CCL24 in this disease.

A blocking monoclonal antibody to CCL24 alleviates liver fibrosis and inflammation in experimental models of liver damage.

Background & Aims: C-C motif chemokine ligand 24 (CCL24) is a chemokine that regulates inflammatory and fibrotic activities through its receptor, C-C motif chemokine receptor (CCR3). The aim of the study was to evaluate the involvement of the CCL24-CCR3 axis in liver fibrosis and inflammation and to assess the potential of its blockade, by a monoclonal anti-CCL24 antibody, as a therapeutic strategy for non-alcoholic steatohepatitis (NASH) and liver fibrosis.

Methods: Expression of CCL24 and CCR3 was evaluated in liver biopsies and blood samples.

Blockade of CCL24 with a monoclonal antibody ameliorates experimental dermal and pulmonary fibrosis.

Objectives: We aimed to assess the expression of the CCL24 chemokine in systemic sclerosis (SSc) and to evaluate the possible pathogenic implications of the CCL24/CCR3 axis using both in vitro and in vivo models. We further investigated the efficacy of an anti-CCL24 monoclonal antibody (mAb), CM-101, in inhibiting cell activation as well as dermal and pulmonary inflammation and fibrosis in experimental animal models.

Methods: We used ELISA and fluorescence immunohistochemistry to determine CCL24 levels in serum and CCL24/CCR3 expression in skin biopsies of SSc patients.

CXCR4 Promotes Neuroblastoma Growth and Therapeutic Resistance through miR-15a/16-1-Mediated ERK and BCL2/Cyclin D1 Pathways.

CXCR4 expression in neuroblastoma tumors correlates with disease severity. In this study, we describe mechanisms by which CXCR4 signaling controls neuroblastoma tumor growth and response to therapy. We found that overexpression of CXCR4 or stimulation with CXCL12 supports neuroblastoma tumorigenesis.

Inflammation-induced hepatocellular carcinoma is dependent on CCR5 in mice.

Unlabelled: Human hepatocellular carcinoma (HCC) is an inflammation-induced cancer, which is the third-leading cause of cancer mortality worldwide. We investigated the role of the chemokine receptors, CCR5 and CCR1, in regulating inflammation and tumorigenesis in an inflammation-induced HCC model in mice. Multidrug resistance 2 gene (Mdr2)-knockout (Mdr2-KO) mice spontaneously develop chronic cholestatic hepatitis and fibrosis that is eventually followed by HCC.

Interstrain differences in chronic hepatitis and tumor development in a murine model of inflammation-mediated hepatocarcinogenesis.

Unlabelled: Chronic inflammation is strongly associated with an increased risk for hepatocellular carcinoma (HCC) development. The multidrug resistance 2 (Mdr2)-knockout (KO) mouse (adenosine triphosphate-binding cassette b4(-/-) ), a model of inflammation-mediated HCC, develops chronic cholestatic hepatitis at an early age and HCC at an adult age. To delineate factors contributing to hepatocarcinogenesis, we compared the severity of early chronic hepatitis and late HCC development in two Mdr2-KO strains: Friend virus B-type/N (FVB) and C57 black 6 (B6).

Ccr5 deficiency regulates the proliferation and trafficking of natural killer cells under physiological conditions.

Chemokines were shown to govern the trafficking of immune cells and may also play important roles in the survival and activation of these cells. We report here that under physiological conditions, the bone marrow (BM), spleen, blood and liver of Ccr5, but not of Ccr1-deficient mice, contain reduced numbers of NK cells. NK cells in the BM of Ccr5-deficient mice proliferate to a lesser extent compared to WT mice.