Down-regulation of IL-12 p40 gene in Plasmodium berghei-infected mice.
We analyzed the mechanism that causes suppression of IL-12 p40 gene induction during Plasmodium berghei infection. Although IL-12 together with IFN-gamma plays an important role in protection against pathogenic infection, the IL-12 p70 protein production of infected macrophages is lower than that by the uninfected macrophages. We showed in the present study that the induction of IL-12 p40 gene but not IL-12 p35 gene in macrophages of P. berghei-infected mice was profoundly inhibited. The inhibition was induced by interaction with macrophages that had contacted with P. berghei-infected erythrocytes and was mediated by a soluble factor, IL-10. There was comparable activation of NF-kappaB in uninfected and infected cells. The induction of IFN-regulatory factor-1 gene was comparable in transcription level in uninfected and infected cells, while the unidentified complex formation of IFN-regulatory factor-1 was observed in infected cells. Therefore, the inhibition of the IL-12 p40 gene induction appeared to be regulated at transcriptional regulation level of the gene.
Xu
X
X
Department of Immunology and Host Defenses, Ehime University School of Medicine, Ehime, Japan.
Sumita
K
K
Feng
C
C
Xiong
X
X
Shen
H
H
Maruyama
S
S
Kanoh
M
M
Asano
Y
Y
D000818:Animals; D001202:Ascitic Fluid / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D015536:Down-Regulation / Q000235:genetics* / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D005786:Gene Expression Regulation / Q000276:immunology*; D050856:Interferon Regulatory Factor-1; D016753:Interleukin-10 / Q000096:biosynthesis / Q000502:physiology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008288:Malaria / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology; D010587:Phagocytosis / Q000276:immunology; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology; D010962:Plasmodium berghei / Q000276:immunology*; D015533:Transcriptional Activation
D018925:Chemokines; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D016177:Macrophage-1 Antigen; D016328:NF-kappa B; D010750:Phosphoproteins; D016753:Interleukin-10; D018664:Interleukin-12