* Ludwig Institute for Cancer Research, São Paulo, Brazil; Departments of
Microbiology, and
Biochemistry and Immunology, UFMG, Minas Gerais, Brazil;
Department of Microbiology, New York University School of Medicine, New York, New York; and
|| Department of Physiology and Pharmacodynamics, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil
Correspondence: Luiz F. L. Reis, Ludwig Institute for Cancer Research, Rua Prof. Antonio Prudente 109, 4th Floor, CEP 01509-010, São Paulo, Brazil. E-mail: lreis{at}ludwig.org.br
Tumor necrosis factor-stimulated gene 14 (TSG-14)/PTX3 was identified
originally as a TNF-
and IL-1ß-stimulated gene from normal, human
foreskin fibroblasts and vascular endothelial cells, respectively.
TSG-14 gene encodes a 42-kDa-secreted glycoprotein with a
carboxy-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 experimental
evidence suggests that TSG-14 plays a role in inflammation, yet its
function and mechanism of action remain unclear. We have generated
transgenic mice that overexpress the murine TSG-14 gene under the
control of its own promoter. From eight transgenic founders, two
lineages were derived and better characterized: Tg2 and Tg4, carrying
two and four copies of the transgene, respectively. TSG-14 transgenic
mice were found to be more resistant to the endotoxic shock induced by
LPS and to the polymicrobial sepsis caused by cecal ligation and
puncture (CLP). Moreover, macrophages derived from the transgenic mice
produced higher amounts of nitric oxide in response to IFN-
,
TNF-, and LPS as compared with macrophages from wild-type animals,
and the augmented response appears to be the consequence of a higher
responsiveness of transgenic macrophages to IFN-. 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.
Key Words: TNF • lipopolysaccharide • endotoxin • inflamma-tion • nitric oxide
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