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Interferon-gamma inhibits expression of the long pentraxin PTX3 in human monocytes
N Polentarutti1, G Picardi, A Basile
1Department of Immunology and Cell Biology, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Abstract:
PTX3 is a prototypic long pentraxin expressed by various cell types, most prominently monocytes and endothelial cells, in response to interleukin-1 (IL-1), tumor necrosis factor (TNF) and bacterial products. In the present report, we show that interferon-gamma (IFN-gamma) inhibits the expression of the PTX3 gene induced by exposure to IL-1, TNF or lipopolysaccharide in human monocytes. This effect is dose dependent and observable when IFN-gamma is added from 24 h before up to 3 h after the addition of IL-1. While the time course of the IL-1-induced PTX3 mRNA expression is not affected, IFN-gamma reduces the stability of the PTX3 mRNA as well as its transcription. The inhibition of PTX3 expression is restricted to monocytes in that no inhibition occurs in cytokine-stimulated fibroblasts and endothelial cells. Under the same conditions, as expected, IFN-gamma augmented monocyte chemotactic protein-1 expression in the same cell preparations. PTX3 protein secretion by activated monocytes is also suppressed by exposure to IFN-gamma. Altogether, these data identify a negative pathway of regulation mediated by IFN-gamma, which may occur under inflammatory conditions.
Insights
Interferon-gamma (IFN-gamma) inhibits PTX3 gene expression in human monocytes, reducing mRNA stability and transcription. This negative regulation pathway may occur during inflammation.
Area of Science:
- Immunology
- Molecular Biology
Background:
- PTX3 is a long pentraxin produced by monocytes and endothelial cells.
- Its expression is induced by inflammatory signals like IL-1, TNF, and bacterial products.
Purpose of the Study:
- To investigate the effect of interferon-gamma (IFN-gamma) on PTX3 gene expression in human monocytes.
- To elucidate the regulatory mechanisms involved in IFN-gamma-mediated inhibition of PTX3.
Main Methods:
- Human monocytes were treated with IL-1, TNF, or lipopolysaccharide (LPS) with or without IFN-gamma.
- PTX3 mRNA levels, stability, and transcription were analyzed.
- PTX3 protein secretion and monocyte chemotactic protein-1 (MCP-1) expression were measured.
Main Results:
- IFN-gamma significantly inhibited IL-1-, TNF-, or LPS-induced PTX3 gene expression in monocytes in a dose-dependent manner.
- IFN-gamma reduced PTX3 mRNA stability and transcription, but not the mRNA expression time course.
- The inhibitory effect was specific to monocytes, with no observed inhibition in fibroblasts or endothelial cells.
- IFN-gamma suppressed PTX3 protein secretion and enhanced MCP-1 expression in monocytes.
Conclusions:
- IFN-gamma acts as a negative regulator of PTX3 expression in human monocytes.
- This regulation occurs at the transcriptional and post-transcriptional (mRNA stability) levels.
- The findings suggest a novel IFN-gamma-mediated inhibitory pathway relevant to inflammatory conditions.