Ar. Goodman et al., Differential regulation of TSG-14 expression in murine fibroblasts and peritoneal macrophages, J LEUK BIOL, 67(3), 2000, pp. 387-395
Tumor necrosis factor (TNF)-stimulated gene 14 (TSG-14, also termed PTX3) e
ncodes a secreted glycoprotein whose carboxyterminal half shares sequence s
imilarity,vith the pentraxin family of acute phase proteins (C-reactive pro
tein and serum amyloid P component). We compared TSG-14 mRNA expression in
cultures of murine BALB/c 3T3 fibroblasts and thioglycollate-elicited perit
oneal macrophages, TNF and interleukin-1 (IL-1) potently induced TSG-14 exp
ression in 3T3 fibroblasts but not in peritoneal macrophages. Lipopolysacch
aride (LPS) elicited TSG-14 expression in both cell types, but induction in
3T3 cells and macrophages shelved several distinct characteristics. Wherea
s in 3T3 fibroblasts TSG-14 mRNA was rapidly up-regulated by LPS, expressio
n in macrophages was substantially delayed, Furthermore, cycloheximide grea
tly reduced LPS-induced TSG-14 mRNA up-regulation in macrophages but not in
3T3 cells, Finally, interferon-gamma (IFN-gamma; but not IFN-alpha/beta) i
nhibited LPS-induced TSG-14 expression in macrophages and not in 3T3 fibrob
lasts, The antioxidant pyrrolidine dithiocarbamate inhibited LPS-induced nu
clear factor-kappa B (NF-kappa B) activation and TSG-14 expression in macro
phages, in contrast, IFN-gamma did not inhibit NF-kappa B function as measu
red by I kappa B-alpha and I kappa B-beta degradation, I kappa B-alpha resy
nthesis, or electrophoretic mobility shift analysis, Inhibition of LPS-indu
ced TSG-14 mRNA expression by IFN-gamma in macrophages was also observed in
the presence of cycloheximide and in cells from STAT1 null mice, suggestin
g that IFN-gamma inhibits TSG-14 expression through an unconventional mecha
nism.