After normalization to GAPDH mRNA levels in each sample, IL-32 mRNA levels of HCV-infected cells were compared with mock-treated cells. No significant induction of IL-32 mRNA could be detected at the early timepoint, whereas 48 hours postinfection IL-32 mRNA levels were increased 11.3-fold. In the present study we describe a novel role for IL-32 in patients with chronic HCV infection.

The levels of IL-32 mRNA were significantly correlated with hepatic inflammation, liver fibrosis, and steatosis. In addition, we demonstrate that IL-32 is endogenously produced by human hepatocyte cell lines and in primary human blood monocytes and is increased upon stimulation RG7204 ic50 with IL-1β and TNF-α. Furthermore, we show that HCV infection of Huh-7.5 cells significantly increases IL-32 expression. Thus, these observations support a potential role for IL-32 in promoting hepatic inflammation and fibrogenesis in chronic HCV infection. selleck inhibitor IL-32 exerts proinflammatory

effects in various cell types including epithelial and endothelial cells as well as mononuclear cells.10, 15 Consistent with these reports, we observed a highly significant association between IL-32 expression and hepatic inflammation. IL-32, a major monocyte/macrophage product, stimulates monocytes and macrophages to induce important proinflammatory cytokines (IL-1β, IL-6, and TNFα) and chemokines (IL-8 and MIP-2) by activating the NF-κB and p38 mitogen-activated protein (MAP) kinase pathways. IL-32 is not only involved in host defense against pathogens, but might play a role in various chronic inflammatory Astemizole diseases as suppression of endogenously

IL-32 impairs production of the proinflammatory cytokines TNF-α and IL-1β.34 This cytokine, namely IL-32, contributes to host responses through the induction of other proinflammatory cytokines but also directly affects specific immunity by differentiating monocytes into macrophage-like cells.35 Importantly, IL-32 even reversed granulocyte-macrophage colony-stimulating factor (GM-CSF)/IL-4-induced dendritic cell differentiation to macrophage-like cells, suggesting that it might indeed reflect a key cytokine for macrophage development.35 Apoptotic cell death is a critical mechanism responsible for liver injury in chronic HCV and additionally contributes to hepatic fibrogenesis. IL-32, which is expressed by primary human keratinocytes, is able to modulate keratinocyte apoptosis, as transfection of primary keratinocytes with siRNA to IL-32 significantly reduced keratinocyte apoptosis.36 A proapoptotic effect for IL-32 was also demonstrated in activated T cells and NK cells. IL-32 was highly expressed in T cells undergoing apoptosis, whereas down-regulation of IL-32 prevented apoptosis.