Suppression of IP-10/CXCL10 gene expression in LPS- and/or IFN-γ-stimulated macrophages by parasite-secreted products

T helper (Th)2 polarized immune responses are characteristically dominant in helminth infections. The gene expression of interferon (IFN)-gamma-inducible protein 10 (IP-10/CXCL10), which promotes Th1 responses, in mouse macrophages stimulated with lipopolysaccharide (LPS) and/or IFN-gamma was suppressed by excretory/secretory (ES) products of Spirometra erinaceieuropaei plerocercoids. ES products suppressed LPS- and/or IFN-gamma-induced transcriptional activities of a luciferase reporter gene under the control of a 243-bp fragment of the IP-10 gene promoter/enhancer, which contains an IFN-stimulated response element (ISRE) and two kappa B elements. Consistent with this result, ES products inhibited ISRE-dependent heterologous promoter activities and LPS- or IFN-gamma-induced ISRE-binding activity. ES products also suppressed LPS-induced IFN-beta gene expression. Furthermore, ES products suppressed nuclear factor (NF)-kappa B RelA (p65)-dependent transcriptional activity, whereas ES products had no effect on the kappa B-binding activity. These results suggest that ES products suppress the IP-10 gene expression by inhibiting the ISRE- and RelA-dependent transcriptional activities in mouse macrophages. (C) 2012 Elsevier Inc. All rights reserved.