Cloning of mouse ptx3, a new member of the pentraxin gene family expressed at extrahepatic sites

Abstract

Pentraxins, which include C reactive protein (CRP) and serum amyloid P component (SAP), are prototypic acute phase reactants that serve as indicators of inflammatory reactions. Here we report genomic and cDNA cloning of mouse ptx3 (mptx3), a member of the pentraxin gene family and characterize its extrahepatic expression in vitro and in vivo. mptx3 is organized into three exons on chromosome 3: the first (43 aa) and second exon (175 aa) code for the signal peptide and for a protein portion with no high similarity to known sequences the third (203 aa) for a domain related to classical pentraxins, which contains the “pentraxin family signature.” Analysis of the N terminal portion predicts a predominantly alpha helical structure, while the pentraxin domain of ptx3 is accommodated comfortably in the tertiary structure fold of SAP. Normal and transformed fibroblasts, undifferentiated and differentiated myoblasts, normal endothelial cells, and mononuclear phagocytes express mptx3 mRNA and release the protein in vitro on exposure to interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF)alpha. mptx3 was induced by bacterial lipopolysaccharide in vivo in a variety of organs and, most strongly, in the vascular endothelium of skeletal muscle and heart. Thus, mptx3 shows a distinct pattern of in vivo expression indicative of a significant role in cardiovascular and inflammatory pathology.

Pentraxin‐3 modulates lipopolysaccharide‐induced inflammatory response and attenuates liver injury

“…1A,B). (37,38) Plasma levels of PTX3 were also increased in compensated alcoholic patients with cirrhosis and further increased in patients with both mild and severe AH (Fig. 7B).…”

“…Although there was a clear positive correlation of PTX3 with disease progression, our in vitro, ex vivo, and in vivo data suggest that PTX3 exerts a hepatoprotective and a modulatory effect on acute-on-chronic inflammatory events, taking into account that PTX3 protein and regulation are conserved between mice and humans. (37,38) This apparently contradictory result suggests that PTX3 might be expressed as a local response to injury and infection by modulating an exacerbated inflammatory response. Moreover, high PTX3 levels in patients could be a counterregulatory response to disease severity.…”

The long pentraxin PTX3: A prototypical sensor of tissue injury and a regulator of homeostasis

“…Moreover, PTX3 primary sequence is highly conserved among animal species (human and murine proteins share 92% of conserved amino acids), suggesting a strong evolutionary pressure to preserve both its structure and function. 55,56 Structurally, PTX3 is a 340 kDa octameric protein, composed by eight identical protomers interacting through both inter-and intra-chain disulphide bonds. 57 Proximal promoters of both human and murine PTX3 gene share several regulatory elements, such as Pu1, SP1, NF-κB, AP-1 and NF-IL-6.…”

Goeckerman's therapy for psoriasis with special reference to serum pentraxin 3 level

“…5 PTX3 is produced by dendritic cells, macrophages, and endothelial cells in response to many inflammatory stimuli. 6 Elevated PTX3 was found in infection, 7 myocardial infarction, 8 and in critically ill patients. 9 Recently, an elevated serum level of PTX3 in patients suffering from psoriasis was described by Bevelacqua et al .…”