The host response to gram-negative endotoxin is characterized by an influx
of inflammatory cells into host tissues, mediated in part by localized prod
uction of chemokines. In this study, using subtractive suppression hybridiz
ation analysis, we demonstrate that ANA-1 murine macrophages produce the CC
chemokine, MIP-1 gamma, in response to LPS-mediated NO production. Gene tr
anscription and protein translation are upregulated in the setting of LPS-i
nduced NO synthesis. However, NO alone is a necessary but insufficient cofa
ctor for induction of MIP-1 gamma protein expression; an NO-independent LPS
signalling pathway is also required. This study suggests a novel mechanism
by which NO modulates the host inflammatory response to endotoxin, (C) 200
0 Academic Press.