Reduced expression of STAT4 and IFN-gamma in macrophages from BALB/c mice.
BALB/c mice have been shown to easily induce Th2 type responses in several infection models. In this study, to examine the mechanisms of Th2 dominant responses in BALB/c mice, we assessed several macrophage functions using C3H/HeN, C57BL/6, and BALB/c mouse strains. Peritoneal macrophages from three strains of mice equally produced IL-12 by stimulation with LPS plus IFN-gamma. However, IFN-gamma production in response to IL-12 or IL-12 plus IL-18 was much lower in macrophages from BALB/c mice than other strains. IFN-gamma produced by activated macrophages induced IL-12R mRNA expression in T cells and macrophages themselves depending on their amount of IFN-gamma; namely, macrophages from BALB/c mice induced lower expression of IL-12R. Intracellular levels of STAT4 were much lower in macrophages from BALB/c mice. However, other STATs, such as STAT1 or STAT6, were expressed similarly in the three mouse strains. STAT4 and IFN-gamma production by other cell types such as T cells and B cells were equal in C3H/HeN and BALB/c mice. These results indicate that macrophages from Th2-dominant BALB/c mice have different functional characters compared with other mouse strains; that is, STAT4 expression and IFN-gamma production are reduced, which is one of the causes to shift to Th2-type responses.
Kuroda
Etsushi
E
Department of Immunology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Kito
Tomohiro
T
Yamashita
Uki
U
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018123:Receptors, Interleukin / Q000096:biosynthesis; D053707:Receptors, Interleukin-12; D050797:STAT4 Transcription Factor; D013601:T-Lymphocytes / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000032:analysis / Q000096:biosynthesis*
D004268:DNA-Binding Proteins; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D015534:Trans-Activators; D007371:Interferon-gamma