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| ROLE OF ENDOGENOUS INTERFERON-BETA IN LIPOPOLYSACCHARIDE-TRIGGERED ACTIVATION OF THE INDUCIBLE NITRIC-OXIDE SYNTHASE GENE IN A MOUSE MACROPHAGE CELL-LINE, J774 |
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| Author(s): FUJIHARA M, ITO N, PACE JL, WATANABE Y, RUSSELL SW, SUZUKI T |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 269 Issue: 17 Pages: 12773-12778 Published: APR 29 1994 |
| Times Cited: 91 References: 42 |
| Abstract: The role of endogenous tumor necrosis factor alpha (TNF-alpha) and interferon-beta (IFN-beta) in lipopolysaccharide (LPS)-induced activation of the inducible nitric-oxide synthase (i-NOS) gene was investigated. By Northern analysis or reverse-transcription polymerase chain reaction, the mouse macrophage cell line (J774) was found to respond to LPS treatment by increased expression of mRNAs specific for TNF-alpha, IFN-beta, and i-NOS with the kinetics unique for each gene. Bioassay of the culture supernatants showed that TNF-alpha and IFN-beta secreted by J774 cells increased from an undetectable level to about 300 and 340 units/ml, respectively, 3-6 h after LPS stimulation. Nitrite concentration was found to increase from 0 to 7.8 and 28.5 mu M by 12 and 24 h, respectively, in the culture supernatant of LPS-treated J774 cells. The presence of a neutralizing dose of antibodies against IFN-beta, but not against TNF-alpha, during treatment with either 10 ng or 1 mu g of LPS/ml significantly, but not completely, decreased the level of i-NOS specific mRNA expression and NO production. The incubation of J774 cells with mouse natural IFN-beta itself (up to the level of 1,200 units/ ml) did not induce i-NOS-specific mRNA and therefore did not stimulate J774 cells to produce NO, However, natural IFN-beta synergistically augmented the expression of i-NOS mRNA and the production of NO by J774 cells triggered by suboptimal concentrations of LPS (1 to 5 ng/ml). These data thus suggest that endogenous IFN-beta, but not TNF-alpha, produced by LPS-stimulated J774 cells specifically contributes, probably in an auto/paracrine fashion, to the activation of the i-NOS gene expression by LPS. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV KANSAS, MED CTR, DEPT MICROBIOL MOLEC GENET & IMMUNOL, KANSAS CITY, KS 66160 USA
2. UNIV KANSAS, MED CTR, DEPT PATHOL & LAB MED, KANSAS CITY, KS 66160 USA
3. UNIV KANSAS, MED CTR, CTR CANC, KANSAS CITY, KS 66160 USA
4. KYOTO UNIV, FAC PHARMACEUT SCI, DEPT MOLEC MICROBIOL, SAKYO KU, KYOTO 606, JAPAN |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: NH716 |
| ISSN: 0021-9258 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |