Abstract |
We previously reported that resting mouse peritoneal macrophages (PM) constitutively express low levels of IFN-gamma, whose production is consistently enhanced by exogenous IFN-gamma. In this study, we investigated the effects of IL-12 on the replication of vesicular stomatitis virus and on IFN-gamma gene expression in mouse PM. The addition of IL-12 to freshly explanted PM resulted in the persistence of an antiviral state to vesicular stomatitis virus, while control PM progressively became permissive for virus replication after 3 to 4 days in culture. The IL-12-induced antiviral state was inhibited by Abs to IFN-gamma, suggesting that endogenous IFN-gamma was largely responsible for this antiviral response. Moreover, IL-12 induced a consistent secretion of IFN-gamma, especially in cultured PM. The IL-1 2-induced antiviral state and IFN-gamma production were observed using PM from various strains of mice, including LPS-defective C3H/HeJ, NK-deficient bg/bg, DBA/2, Swiss (CD1), and Swiss nude mice treated or not with anti- asialo GM1 Abs. A 4-h treatment with IL-12 was sufficient to induce a marked accumulation of IFN-gamma mRNA, which was greater in cultured PM than in freshly harvested cells. Lastly, immunofluorescence studies in IL-12-stimulated macrophages clearly showed an enhancement of immunoreactive IFN-gamma compared with basal levels in cells exhibiting a macrophage (i.e., F4/80-positive) phenotype. Together, these findings demonstrate that IL-12 can directly stimulate mouse PM to produce IFN-gamma. We suggest that IL-12-induced IFN-gamma production by macrophages can play some role in the generation of the antiviral and immunoregulatory effects of IL-12.
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Authors | P Puddu, L Fantuzzi, P Borghi, B Varano, G Rainaldi, E Guillemard, W Malorni, P Nicaise, S F Wolf, F Belardelli, S Gessani |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 159
Issue 7
Pg. 3490-7
(Oct 01 1997)
ISSN: 0022-1767 [Print] United States |
PMID | 9317148
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies
- Antigens, Differentiation
- Antiviral Agents
- RNA, Messenger
- monocyte-macrophage differentiation antigen
- Interleukin-12
- G(M1) Ganglioside
- asialo GM1 ganglioside
- Interferon-gamma
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Topics |
- Animals
- Antibodies
(pharmacology)
- Antigens, Differentiation
(analysis)
- Antiviral Agents
(pharmacology)
- Cells, Cultured
- G(M1) Ganglioside
(immunology)
- Interferon-gamma
(biosynthesis, genetics, metabolism, physiology)
- Interleukin-12
(pharmacology)
- Intracellular Fluid
(immunology)
- Macrophages, Peritoneal
(immunology, metabolism, virology)
- Male
- Mice
- Mice, Inbred C3H
- Mice, Inbred DBA
- Mice, Nude
- RNA, Messenger
(biosynthesis, drug effects)
- Species Specificity
- Tumor Cells, Cultured
- Vesicular stomatitis Indiana virus
(drug effects, immunology)
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