IL-5 but not interferon-gamma (IFN-gamma) inhibits eosinophil apoptosis by up-regulation of bcl-2 expression.
In order to determine regulatory mechanisms of eosinophil apoptosis, we examined the effect of recombinant IL-5 and interferon-gamma (IFN-gamma) on eosinophil apoptosis and bcl-2 expression. rhIL-5 (2.5 ng/ml) significantly inhibited eosinophil apoptosis in 96 h in vitro culture compared with medium only-cultured eosinophils (89.4 +/- 3.6% versus 31.3 +/- 12.2% (mean +/- s.d.); n = 7, P < 0.05). Further, rhIL-5 significantly increased bcl-2 protein and mRNA expression on cultured eosinophils. A phosphorothioate antisense oligonucleotide targeted at the ATG translation initiation codon of bcl-2 (10(-5) M) could significantly block the supportive effect of rhIL-5 (0.25 ng/ml) for eosinophil survival compared with sense cDNA of bcl-2 on 96 h culture (inhibition rate 28.01 +/- 4.56% versus 0.07 +/- 1.73%; n = 4, P < 0.05). In contrast, rhIFN-gamma (100 U/ml) significantly inhibited eosinophil apoptosis on 96 h in vitro culture (72.7 +/- 10.5%; n = 7, P < 0.05), but did not significantly up-regulate bcl-2 protein and mRNA. These results indicate that IL-5 has inhibitory effects on eosinophil apoptosis by regulation of bcl-2 expression.
Ochiai
K
K
Department of Internal Medicine, Toho University School of Medicine, Sakura Hospital, Chiba, Japan.
Kagami
M
M
Matsumura
R
R
Tomioka
H
H
D017209:Apoptosis / Q000187:drug effects*; D004804:Eosinophils / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000819:agonists* / Q000096:biosynthesis* / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000502:physiology*
D015848:Interleukin-5; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D007371:Interferon-gamma