Augmentation of lipopolysaccharide-induced thymocyte apoptosis by interferon-gamma.
The role of interferon (IFN)-gamma on thymocyte apoptosis in response to lipopolysaccharide (LPS) was investigated. The administration of LPS into mice induced marked apoptosis of thymocytes in vivo, but the simultaneous injection of anti-IFN-gamma antibody with LPS completely prevented thymocyte apoptosis. Pretreatment of mice with IFN-gamma markedly enhanced LPS-induced thymocyte apoptosis. Thymocyte apoptosis augmented by IFN-gamma occurred in the thymic cortex, and target cells undergoing apoptosis were CD4+8+ immature thymocytes. IFN-gamma itself did not induce thymocyte apoptosis in vivo and in vitro. IFN-gamma exhibited no synergistic action with effector molecules, such as tumor necrosis factor (TNF)-alpha and glucocorticoids. Further, it was shown that IFN-gamma did not enhance the susceptibility of thymocytes to apoptosis. Pretreatment of mice with IFN-gamma significantly augmented the serum TNF-alpha level and the serum cortisol level in response to LPS. Therefore, we suggest that IFN-gamma might augment LPS-induced thymocyte apoptosis through elevating serum TNF-alpha and cortisol levels.
Kato
Y
Y
Department of Microbiology and Immunology, Aichi Medical University, Nagakute, Japan.
Morikawa
A
A
Sugiyama
T
T
Koide
N
N
Jiang
G Z
GZ
Lwin
T
T
Yoshida
T
T
Yokochi
T
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004357:Drug Synergism; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000494:pharmacology
D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D006854:Hydrocortisone