Disease relevance of Ptx3

• Ptx3-null mice were susceptible to invasive pulmonary aspergillosis [1].
• Here, we report that the infertility of Ptx3(-/-) mice is associated with severe abnormalities of the cumulus oophorus and failure of in vivo, but not in vitro, oocyte fertilization [2].
• Recently, we demonstrated that TSG-14 transgenic mice (TSG-14tg) overexpressing the murine TSG-14 gene under control of its own promoter are more resistant to lipopolysaccharide-induced shock and to polymicrobial sepsis caused by cecal ligation and puncture [3].
• The data shown here are the first in vivo evidence of the involvement of TSG-14 in the inflammatory process and suggest a role for TSG-14 in the defense against bacterial infections [4].
• We also clearly observed PTX3-positive neutrophils infiltrating into atherosclerotic plaques, suggesting that PTX3 derived from neutrophils as well as macrophages plays an important role in atherogenesis [5].

High impact information on Ptx3

• Ptx3 binds selected microbial agents, including conidia of Aspergillus fumigatus, and we found that susceptibility of Ptx3-null mice was associated with defective recognition of conidia by alveolar macrophages and dendritic cells, as well as inappropriate induction of an adaptive type 2 response [1].
• In contrast, Wnt-5a primarily increased the proportion of Nurr1+ precursors that acquired a neuronal DA phenotype and up-regulated the expression of Ptx3 and c-ret mRNA [6].
• In addition, the expression of additional pattern recognition receptors, including TLR9, pentraxin-3, and lectin-like oxidized LDL receptor-1, was regulated, in part, via a MyD88-dependent manner as demonstrated by the attenuated expression of these receptors in MyD88 KO microglia [7].
• These results demonstrate that transgenic expression of TSG-14 induces an enhanced local and systemic injury and TNF-alpha-dependent lethality after I/R [3].
• TSG-14/PTX3 is a gene inducible by tumor necrosis factor (TNF)-alpha, interleukin-1 beta, and lipopolysaccharide in fibroblasts, macrophages, and endothelial cells [3].

Chemical compound and disease context of Ptx3

• Here we examined the protective effects of administration of PTX3 alone or together with deoxycholate amphotericin B (Fungizone) or liposomal amphotericin B (AmBisome) against invasive aspergillosis in a murine model of allogeneic bone marrow transplantation [8].

Biological context of Ptx3

• To define PTX3 function during ovulation, we generated knockout mice lacking the Ptx3 gene [9].
• Our results provide evidence for a role of PTX3 as an important component of the innate-immune response and as part of the host mechanisms that control fungal recognition and phagocytosis [10].
• Promoter structure and transcriptional activation of the murine TSG-14 gene encoding a tumor necrosis factor/interleukin-1-inducible pentraxin protein [11].
• The promoter of the TSG-14 gene lacks consensus sequences for either a TATA box or CCAAT box [11].
• Analysis of the coding region predicts a high degree of amino acid sequence homology between murine and human TSG-14 (88 and 75% identity in the first and second exons, respectively) [11].

Anatomical context of Ptx3

• Recombinant (r)PTX3 protein binds to Zy particles as well as to yeast cells of P. brasiliensis and addition of rPTX3, to a culture of WT-derived macrophages containing Zy leads to an increase in the phagocytic index, which parallels that of Tg-derived macrophages, demonstrating the opsonin-like activity of PTX3 [10].
• Here, we show that peritoneal macrophages derived from PTX3 transgenic (Tg) mice express higher levels of PTX3 mRNA than macrophages from wild-type (WT) mice, at basal level as well as upon stimulation with zymosan (Zy) [10].
• We recently isolated a homeodomain transcription factor, named Ptx3, that is uniquely expressed in the dopaminergic neurons of the substantia nigra pars compacta and ventral tegmental area, which together form the mesencephalic dopaminergic system [12].
• Differential expression of pentraxin 3 in fibroblasts from patients with major depression [13].
• Lipopolysaccharide (LPS) elicited TSG-14 expression in both cell types, but induction in 3T3 cells and macrophages showed several distinct characteristics [14].

Associations of Ptx3 with chemical compounds

• Human TNF-stimulated gene 14 (TSG-14) encodes a secreted 42-kDa glycoprotein that shows significant homology to proteins of the pentraxin family, which includes the acute phase reactants C-reactive protein and serum amyloid P component [11].
• These include the homeobox transcription factors engrailed and Ptx-3 as well as aldehyde dehydrogenase 2, here defined as the earliest marker identified in developing DA cells, expressed already in mitotic DA progenitors [15].
• A moderate increase in TSG-14 mRNA was observed in FS-4 cells treated with the glucocorticoid dexamethasone [16].
• Similarly, at 19 weeks we detected no significant elevation of transcripts for the APPs serum amyloid A, complement C3, pentraxin 3, and alpha2-antiplasmin in the liver, despite CNS neurodegeneration and splenic PrPSc deposition at this time [17].
• TNF and interleukin-1 (IL-1) potently induced TSG-14 expression in 3T3 fibroblasts but not in peritoneal macrophages [14].

Regulatory relationships of Ptx3

• It is important that blockade of dectin-1 receptor inhibited the phagocytosis of Zy particles by WT and PTX3 Tg macrophages, pointing out the relevant role of dectin-1 as the main receptor involved in Zy uptake [10].

Other interactions of Ptx3

• Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility [9].
• Whereas Tnfip6 is induced in all granulosa cells by the LH surge, Ptx3 expression in the ovary is specifically observed after the LH surge in the cumulus granulosa cells adjacent to the oocyte [9].
• PTX3 function as an opsonin for the dectin-1-dependent internalization of zymosan by macrophages [10].
• Taken together, our data point to a critical role of TSG-14 in controlling acute inflammatory response in part via the modulation of TNF-alpha expression [3].
• Finally, interferon-gamma (IFN-gamma; but not IFN-alpha/beta) inhibited LPS-induced TSG-14 expression in macrophages and not in 3T3 fibroblasts [14].

Analytical, diagnostic and therapeutic context of Ptx3

• Real-time quantitative polymerase chain reaction (PCR) on selected genes revealed that pentraxin-3, was upregulated by IL-1beta in wild-type, but not in IL-1R1-/- mixed glia [18].

References