IL-12 induces IFN-gamma expression and secretion in mouse peritoneal macrophages.

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.
AuthorsP Puddu, L Fantuzzi, P Borghi, B Varano, G Rainaldi, E Guillemard, W Malorni, P Nicaise, S F Wolf, F Belardelli, S Gessani
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 159 Issue 7 Pg. 3490-7 (Oct 1 1997) ISSN: 0022-1767 [Print] UNITED STATES
PMID9317148 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies
  • Antigens, Differentiation
  • Antiviral Agents
  • RNA, Messenger
  • monocyte-macrophage differentiation antigen
  • Interleukin-12
  • G(M1) Ganglioside
  • asialo GM1 ganglioside
  • Interferon-gamma
  • Animals
  • Antibodies (pharmacology)
  • Antigens, Differentiation (analysis)
  • Antiviral Agents (pharmacology)
  • Cells, Cultured
  • G(M1) Ganglioside (immunology)
  • Interferon-gamma (biosynthesis, genetics, physiology, secretion)
  • Interleukin-12 (pharmacology)
  • Intracellular Fluid (immunology)
  • Macrophages, Peritoneal (immunology, secretion, 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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