title: Apoptosis of intestinal intraepithelial lymphocytes induced by exogenous and endogenous glucocorticoids.
abstract: To investigate the effect of glucocorticoids on apoptosis in intestinal intraepithelial lymphocytes (i-IEL), we examined the changes of i-IEL followed by in vivo treatment with dexamethasone. The fragmented DNA of i-IEL were significantly increased at 15 hr after dexamethasone treatment and, subsequently, the number of total i-IEL were decreased by day 4 after treatment. Although all subsets of i-IEL including CD8 alpha/alpha(+), CD8 alpha/beta(+), CD4+ and CD4+CD8+ i-IEL were decreased after dexamethasone treatment, CD8 alpha/alpha(+) i-IEL appeared to be relatively resistant to dexamethasone-induced apoptosis. Consistent with the in vivo findings, CD8 alpha/alpha(+) i-IEL exhibited less susceptibility to dexamethasone-induced cell death in vitro than other subsets. To investigate whether this process occurs under physiological conditions, we examined the kinetics of i-IEL after treatment with 15-hr water immersion stress. In mice subjected to water immersion stress, plasma glucocorticoids were remarkably elevated soon after the 15-hr stress. The increase in the fragmented DNA of i-IEL and subsequent decrease in the number of i-IEL were observed in the stressed mice in the same kinetics as seen in the dexamethasone-treated mice. Similar to dexamethasone-induced ell death, CD8 alpha/alpha(+) i-IEL appeared to be relatively resistant to stress-induced apoptosis compared with other i-IEL subsets. The expression level of Bcl-2 was significantly higher in CD8 alpha/alpha(+) i-IEL than in CD8 alpha/beta(+) i-IEL. Our results indicate that i-IEL are subjected to cell death via apoptosis by exogenous and endogenous glucocorticoids and that different sensitivity to steroid-induced apoptosis may exist among i-IEL subsets in relation to their Bcl-2 expression.
authors.affiliation: Laboratory of Germfree Life, Nagoya University School of Medicine, Aichi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Murosaki
authors.forename: K
authors.initials: K
authors.lastname: Inagaki-Ohara
authors.forename: H
authors.initials: H
authors.lastname: Kusaka
authors.forename: H
authors.initials: H
authors.lastname: Ikeda
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshikai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D003345:Corticosterone / Q000097:blood / Q000378:metabolism* / Q000502:physiology*; D053938:DNA Fragmentation; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000494:pharmacology*; D007421:Intestine, Small / Q000276:immunology*; D007700:Kinetics; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D015701:Near Drowning / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D005938:Glucocorticoids; D019253:Proto-Oncogene Proteins c-bcl-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003907:Dexamethasone; D003345:Corticosterone