IL-7 prevents both caspase-dependent and -independent pathways that lead to the spontaneous apoptosis of i-IEL.
Intestinal intraepithelial lymphocytes (i-IEL) readily undergo spontaneous apoptosis in vitro through an unclear mechanism. Here we examined the relationship between caspases, which plays a major role in apoptosis, and IL-7 in the spontaneous apoptosis of i-IEL in vitro. We demonstrated that IL-7 and zVAD prevented the spontaneous apoptosis of i-IEL by approximately 50% and 25% respectively with no additive protection seen when both are used. IL-7 preferentially prevented the apoptosis of gammadelta i-IEL, while zVAD equally prevented the apoptosis of gammadelta and alphabeta i-IEL. Lastly, we demonstrated that the spontaneous apoptosis of i-IEL is associated with a marked increase in caspase activity. Caspase activity was completely inhibited by zVAD, but only slightly by IL-7. Overall these results suggest that two pathways lead to the spontaneous apoptosis of i-IEL, one which is caspase dependent and the other which is caspase independent. IL-7 appears to exert its effect on i-IEL undergoing spontaneous by partially inhibiting both apoptotic pathways.
Yada
S
S
Department of Immunology, Kyushu University, Fukuoka, 812-8582, Japan
Nukina
H
H
Kishihara
K
K
Takamura
N
N
Yoshida
H
H
Inagaki-Ohara
K
K
Nomoto
K
K
Lin
T
T
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D053148:Caspase 3; D020169:Caspases / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology; D019409:Interleukin-15 / Q000276:immunology / Q000494:pharmacology; D015851:Interleukin-7 / Q000276:immunology* / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000590:Amino Acid Chloromethyl Ketones; D019409:Interleukin-15; D015851:Interleukin-7; D019253:Proto-Oncogene Proteins c-bcl-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases