Interferon‐γ 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‐γ (IFN‐γ) 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‐γ 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‐γ 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‐γ augmented monocyte chemotactic protein‐1 expression in the same cell preparations. PTX3 protein secretion by activated monocytes is also suppressed by exposure to IFN‐γ. Altogether, these data identify a negative pathway of regulation mediated by IFN‐γ, which may occur under inflammatory conditions.

[1]  M. Pepys,et al.  Acute phase proteins with special reference to C-reactive protein and related proteins (pentaxins) and serum amyloid A protein. , 1983, Advances in immunology.

[2]  E. Fuchs,et al.  Complementary DNA sequence of a human cytoplasmic actin. Interspecies divergence of 3' non-coding regions. , 1983, Journal of molecular biology.

[3]  A. Mantovani,et al.  Rapid killing of actinomycin D-treated tumor cells by human mononuclear cells. I. Effectors belong to the monocyte-macrophage lineage. , 1984, Journal of immunology.

[4]  R. Bast,et al.  Treatment of murine peritoneal macrophages with bacterial lipopolysaccharide alters expression of c-fos and c-myc oncogenes. , 1986, Journal of immunology.

[5]  R. Bast,et al.  Homologous and heterologous desensitization of proto‐oncogene cfos expression in murine peritoneal macrophages , 1987, Journal of cellular physiology.

[6]  E. Dejana,et al.  Fibronectin and vitronectin regulate the organization of their respective Arg-Gly-Asp adhesion receptors in cultured human endothelial cells , 1988, The Journal of cell biology.

[7]  M. Yamada,et al.  Cloning and sequencing of the cDNA for human monocyte chemotactic and activating factor (MCAF). , 1989, Biochemical and biophysical research communications.

[8]  D. Radzioch,et al.  c-fos mRNA expression in macrophages is downregulated by interferon-gamma at the posttranscriptional level. , 1991, Molecular and cellular biology.

[9]  V. Kolb‐Bachofen A review on the biological properties of C-reactive protein. , 1991, Immunobiology.

[10]  M. Rocchi,et al.  Interleukin-1-inducible genes in endothelial cells. Cloning of a new gene related to C-reactive protein and serum amyloid P component. , 1992, The Journal of biological chemistry.

[11]  A. Mantovani,et al.  Expression of a monocyte chemotactic cytokine by human mononuclear phagocytes. , 1992, Journal of immunology.

[12]  J. Vilček,et al.  Downregulation of interleukin 8 gene expression in human fibroblasts: unique mechanism of transcriptional inhibition by interferon. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[13]  J. Vilček,et al.  TSG-14, a tumor necrosis factor- and IL-1-inducible protein, is a novel member of the pentaxin family of acute phase proteins. , 1993, Journal of immunology.

[14]  G. Gusella,et al.  IL-2 Up-regulates but IFN-γ suppresses IL-8 expression in human monocytes , 1993 .

[15]  P. Sharp,et al.  Identification of a novel member of the pentrax in family in Xenopus laevis , 1993, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[16]  I. Kushner Regulation of the Acute Phase Response by Cytokines , 2015, Perspectives in biology and medicine.

[17]  C. Blobel,et al.  Apexin, an acrosomal pentaxin. , 1994, The Journal of biological chemistry.

[18]  A. Whitehead,et al.  The major acute phase reactants: C-reactive protein, serum amyloid P component and serum amyloid A protein. , 1994, Immunology today.

[19]  J. Vilček,et al.  Relationship of TSG-14 protein to the pentraxin family of major acute phase proteins. , 1994, Journal of immunology.

[20]  J. Gauldie,et al.  The acute phase response. , 1994, Immunology today.

[21]  Y. Ohmori,et al.  IFN-gamma selectively inhibits lipopolysaccharide-inducible JE/monocyte chemoattractant protein-1 and KC/GRO/melanoma growth-stimulating activity gene expression in mouse peritoneal macrophages. , 1994, Journal of immunology.

[22]  G. Gerton,et al.  The sperm acrosomal matrix contains a novel member of the pentaxin family of calcium-dependent binding proteins. , 1994, The Journal of biological chemistry.

[23]  J. Helms,et al.  Neuronal pentraxin, a secreted protein with homology to acute phase proteins of the immune system , 1995, Neuron.

[24]  T. Lint,et al.  Structure and function of the pentraxins. , 1995, Current opinion in immunology.

[25]  Y. Hsu,et al.  Human neuronal pentraxin II (NPTX2): conservation, genomic structure, and chromosomal localization. , 1995, Genomics.

[26]  R. Strieter,et al.  Interferon‐α and interferon‐γ down‐regulate the production of interleukin‐8 and ENA‐78 in human monocytes , 1995, Journal of leukocyte biology.

[27]  T. Blundell,et al.  Cloning of mouse ptx3, a new member of the pentraxin gene family expressed at extrahepatic sites. , 1996, Blood.

[28]  C. Barnes,et al.  Narp, a novel member of the pentraxin family, promotes neurite outgrowth and is dynamically regulated by neuronal activity , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[29]  Francesco Tedesco,et al.  Multimer Formation and Ligand Recognition by the Long Pentraxin PTX3 , 1997, The Journal of Biological Chemistry.

[30]  A. Mantovani,et al.  Expression of a long pentraxin, PTX3, by monocytes exposed to the mycobacterial cell wall component lipoarabinomannan , 1997, Infection and immunity.