Produção Nacional
Revisado por pares
TSG-14 transgenic mice have improved survival to endotoxemia and to CLP-induced sepsis
2001; Oxford University Press; Volume: 69; Issue: 6 Linguagem: Inglês
10.1189/jlb.69.6.928
ISSN1938-3673
AutoresAdriana Abalen Martins Dias, Adam R. Goodman, Jane Lima dos Santos, Rachel Novaes Gomes, Anne Altmeyer, Patrı́cia T. Bozza, María de Fátima Horta, J Vilček, Luiz F. L. Reis,
Tópico(s)Biomarkers in Disease Mechanisms
ResumoAbstract Tumor necrosis factor-stimulated gene 14 (TSG-14)/PTX3 was identifiedoriginally as a TNF-α and IL-1β-stimulated gene from normal, humanforeskin fibroblasts and vascular endothelial cells, respectively. TSG-14 gene encodes a 42-kDa-secreted glycoprotein with acarboxy-terminal half that shares homology with the entire sequence of C-reactive protein (CRP) and serum amyloid P component (SAP),acute-phase proteins of the pentraxin family. Some experimentalevidence suggests that TSG-14 plays a role in inflammation, yet itsfunction and mechanism of action remain unclear. We have generatedtransgenic mice that overexpress the murine TSG-14 gene under thecontrol of its own promoter. From eight transgenic founders, twolineages were derived and better characterized: Tg2 and Tg4, carryingtwo and four copies of the transgene, respectively. TSG-14 transgenicmice were found to be more resistant to the endotoxic shock induced byLPS and to the polymicrobial sepsis caused by cecal ligation andpuncture (CLP). Moreover, macrophages derived from the transgenic miceproduced higher amounts of nitric oxide in response to IFN-γ,TNF-α, and LPS as compared with macrophages from wild-type animals, and the augmented response appears to be the consequence of a higherresponsiveness of transgenic macrophages to IFN-γ. The data shownhere are the first in vivo evidence of the involvement of TSG-14 in the inflammatory process and suggest a role for TSG-14 in thedefense against bacterial infections.
Referência(s)