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.
Puddu
P
P
Laboratorie of Immunology, Istituto Superiore di Sanità, Rome, Italy.
Fantuzzi
L
L
Borghi
P
P
Varano
B
B
Rainaldi
G
G
Guillemard
E
E
Malorni
W
W
Nicaise
P
P
Wolf
S F
SF
Belardelli
F
F
Gessani
S
S
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000943:Antigens, Differentiation / Q000032:analysis; D000998:Antiviral Agents / Q000494:pharmacology; D002478:Cells, Cultured; D005677:G(M1) Ganglioside / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D018664:Interleukin-12 / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D013045:Species Specificity; D014407:Tumor Cells, Cultured; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000276:immunology
D000906:Antibodies; D000943:Antigens, Differentiation; D000998:Antiviral Agents; D012333:RNA, Messenger; C036763:monocyte-macrophage differentiation antigen; D018664:Interleukin-12; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D007371:Interferon-gamma