Interleukin-9 is a major anti-apoptotic factor for thymic lymphomas.
We have recently shown that interleukin-9 (IL-9) strongly stimulates the proliferation of mouse thymic lymphomas in vitro. Here we report that this factor is also one of the most potent inhibitors of apoptosis induced by dexamethasone (DEX) in such cell lines, even if they do not depend on exogenous factors for growth. For the murine thymic lymphoma BW5147, protection against apoptosis was also obtained with IL-4 and less strongly with IL-6, whereas IL-2, IL-7, and IL-10 were inactive. Moreover, IL-4 and IL-9 maintained proliferation of these cells in the presence of DEX. Analysis of eight other factor-independent thymic lymphoma lines showed significant protection in seven and six cell lines with IL-9 and IL-4, respectively, whereas only three were protected by IL-7 and only two by IL-2. Comparison of the responses to IL-2 and IL-9 in a factor-dependent cell line that responds to both cytokines showed that IL-2 is a stronger inducer of proliferation, while IL-9 is more efficient in protecting the cells against apoptosis. Taken together, our observations suggest that, for thymic lymphomas, proliferation and apoptosis involve distinct regulatory mechanisms and can be differentially regulated by cytokines.
Ludwig Institute for Cancer Research, Brussels, Belgium.
J C
JC
Renauld
A
A
Vink
J
J
Louahed
J
J
Van Snick
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000032:analysis; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D016906:Interleukin-9 / Q000494:pharmacology / Q000502:physiology*; D008223:Lymphoma / Q000139:chemically induced / Q000209:etiology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D009381:Neoplasms, Radiation-Induced / Q000473:pathology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine; D013953:Thymus Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000470:Alkaloids; D004273:DNA, Neoplasm; D007376:Interleukin-2; D015851:Interleukin-7; D016906:Interleukin-9; D015847:Interleukin-4; D003907:Dexamethasone; D016572:Cyclosporine; D011493:Protein Kinase C; D019311:Staurosporine