Reduced expression of c-Fos in female NOD mouse thymocytes and up-regulation with human lymphotoxin.
Previously we reported that the administration of human (h) lymphotoxin (h-LT) markedly protected NOD mice from insulin-dependent diabetes mellitus (IDDM) partly by affecting the generation phase of anti-islet effector cells, probably in the thymus. In this study, we investigated the effect of h-LT on the signal transduction of the mouse thymocytes by observing c-Fos expression in the thymocytes by using a flow cytometer. The intensity of c-Fos expression in whole thymocytes was significantly lower in the female NOD with a high incidence of diabetes than that in the male NOD mice with a low incidence of diabetes and than that in normal mice (P < 0.0001). The low c-Fos expression in the female NOD thymocytes was most prominent in CD3low thymocytes. c-Jun expression of the CD3low thymocytes was also lower in the female NOD mice. Administrations of h-LT, h-TNF, and h-IL-2, which has been reported to prevent IDDM in NOD mice by systemic administration, significantly up-regulated c-Fos expression in CD3low thymocytes. From these results, it is assumed that a relationship may exist between the high diabetes incidence and the defective c-Fos expression in female NOD mice and between the prevention of IDDM and the amelioration of the defective c-Fos expression with h-LT in female NOD mice.
Takahashi
K
K
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Satoh
J
J
Sagara
M
M
Muto
G
G
Muto
Y
Y
Fukuzawa
M
M
Nishimura
S
S
Miyaguchi
S
S
Qiang
X L
XL
Kumagai
K
K
D000818:Animals; D016207:Cytokines / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation; D008233:Lymphotoxin-alpha / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016688:Mice, Inbred NOD / Q000276:immunology* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D015398:Signal Transduction; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism
D016207:Cytokines; D008233:Lymphotoxin-alpha; D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1