Activation of caspase-3 by interferon alpha causes interleukin-16 secretion but fails to modulate activation induced cell death.
Interferon alpha (IFN-alpha) is the mainstay in the treatment of chronic hepatitis C virus (HCV) infection. Interleukin-16 (IL-16) attracts CD4+ cells to sites of inflammation and plays a role in the interaction of dendritic cells, T cells and B cells. In this study, we show that IFN-alpha itself induces IL-16 secretion by peripheral blood lymphocytes (PBL) and enhances IL-16 secretion by anti-CD3 stimulated PBL. Pro-IL-16 is cleaved into its active form by caspase-3. IFN-alpha increases caspase-3 mRNA levels in activated T cells (ATC), as shown by Northern blot analysis, whereas IL-16 mRNA levels are not affected by IFN-alpha. IL-16 secretion into culture supernatants correlates tightly with intracellular caspase-3 activity in ATC. In our experiments addition of specific caspase inhibitors did not reduce the proportion of ATC undergoing Fas-mediated cell death, but completely blocked IFN-alpha-induced IL-16 secretion into culture supernatants. In conclusion, our results suggest that IFN-alpha activates caspase-3, thereby increasing secretion of IL-16, whereas IFN-alpha-enhanced Fas-mediated cell death in ATC is not caspase-dependent.
Ludwiczek
O
O
Department of Medicine, Division of Gastroenterology and Hepatology, University Hospital Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
Kaser
A
A
Koch
R O
RO
Vogel
W
W
Cruikshank
W W
WW
Tilg
H
H
D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism* / Q000494:pharmacology; D019410:Interleukin-16 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism
D000906:Antibodies; D017252:CD3 Complex; D004791:Enzyme Inhibitors; D016898:Interferon-alpha; D019410:Interleukin-16; D012333:RNA, Messenger; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases