PT  - JOURNAL ARTICLE
AU  - Gao, Jian Jun
AU  - Zuvanich, Eleanor G.
AU  - Xue, Qiao
AU  - Horn, David L.
AU  - Silverstein, Richard
AU  - Morrison, David C.
TI  - Cutting Edge: Bacterial DNA and LPS Act in Synergy in Inducing Nitric Oxide Production in RAW 264.7 Macrophages
DP  - 1999 Oct 15
TA  - The Journal of Immunology
PG  - 4095--4099
VI  - 163
IP  - 8
4099  - http://www.jimmunol.org/content/163/8/4095.short
4100  - http://www.jimmunol.org/content/163/8/4095.full
SO  - J. Immunol.1999 Oct 15; 163
AB  - LPS is well recognized for its potent capacity to activate mouse macrophages to produce NO, an important inflammatory mediator in innate host defense. We demonstrate here that, although inducing little NO alone, DNA from both Gram-negative and Gram-positive bacteria synergizes with subthreshold concentrations of LPS (0.3 ng/ml) to induce NO in cultures of RAW 264.7 macrophages. The effects of the DNA are mimicked by synthetic CpG-containing oligodeoxynucleotides but not by non-CpG-containing oligodeoxynucleotides. This synergistic activity is not inhibited by neutralizing Abs against IFN. Preincubation of macrophages with DNA for 8–24 h suppresses subsequent synergistic macrophage responses to DNA/LPS, whereas prolonged pretreatment with LPS enhances synergy. RT-PCR analysis indicates that the mRNA levels of the inducible NO synthase gene are also coordinately suppressed or induced. These findings indicate that temporally controlled, synergistic interactions exist between microbial DNA and LPS in the induction of macrophage NO via enhanced inducible NO synthase gene expression.