Interferon-gamma inhibits expression of the long pentraxin PTX3 in human monocytes.
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.
Polentarutti
N
N
Department of Immunology and Cell Biology, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Picardi
G
G
Basile
A
A
Cenzuales
S
S
Rivolta
A
A
Matteucci
C
C
Peri
G
G
Mantovani
A
A
Introna
M
M
D002097:C-Reactive Protein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006207:Half-Life; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D000683:Serum Amyloid P-Component / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D000099153:Pentraxins
D002097:C-Reactive Protein; D018932:Chemokine CCL2; D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D012333:RNA, Messenger; D000683:Serum Amyloid P-Component; D000099153:Pentraxins