INTERFERON-GAMMA INHIBITS EXPRESSION OF THE LONG PENTRAXIN PTX3 IN HUMAN MONOCYTES

PTX3 is a prototypic long pentraxin expressed by various cell types, m ost prominently monocytes and endothelial cells, in response to interl eukin-l (IL-l), tumor necrosis factor (TNF) and bacterial products. In the present report, we show that interferon-gamma (IFN-gamma) inhibit s the expression of the PTX3 gene induced by exposure to II-I,TNF or l ipopolysaccharide in human monocytes. This effect is dose dependent an d observable when IFN-gamma is added from 24 h before up to 3 h after the addition of IL-l. While the time course of the IL-l-induced PTX3 m RNA expression is not affected, IFN-gamma( reduces the stability of th e PTX3 mRNA as well as its transcription. The inhibition of PTX3 expre ssion is restricted to monocytes in that no inhibition occurs in cytok ine-stimulated fibroblasts and endothelial cells. Under the same condi tions, as expected, IFN-gamma augmented monocyte chemotactic protein-1 expression in the same cell preparations. PTX3 protein secretion by a ctivated monocytes is also suppressed by exposure to IFN-gamma. Altoge ther, these data identify a negative pathway of regulation mediated by IFN-gamma, which may occur under inflammatory conditions.