Differential effects of IL-15 and IL-21 in myeloid (CD11b+) and lymphoid (CD11b-) bone marrow cells.
IL-15 has been found to activate NF-kappaB in various types of cells. However, the role of this transcription factor in IL-15- and IL-21-stimulated murine bone marrow (BM) cells is unclear. In this study, we demonstrated that both IL-15 and IL-21 are capable of delaying BM cell factor deprivation-induced apoptosis, but only IL-15 induced their proliferation. Following separation of BM cells into myeloid (CD11b(+)) and lymphoid (CD11b(-)) cell populations, we found that IL-15, but not IL-21, significantly induced proliferation in both cell populations. Both cytokines significantly delayed apoptosis, but only in CD11b(-) BM cells. IL-15Ralpha, CD122 (IL-2/15Rbeta), and common gamma-chains (CD132) were expressed in both populations, whereas IL-21Ralpha was expressed only in CD11b(-) BM cells. In addition, we demonstrated that IL-15-induced BM cell proliferation was significantly inhibited in NF-kappaBp50(-/-) mice when compared with littermate controls. The ability of IL-15 and IL-21 to delay BM cell apoptosis was slightly inhibited in NF-kappaBp50(-/-) mice, whereas the antiapoptotic effect of LPS was markedly reversed. We conclude that IL-15, but not IL-21, induces BM cell proliferation and that both cytokines delay BM cell apoptosis. These biological activities were preferentially observed in CD11b(-) BM cells. Using NF-kappaBp50(-/-) mice, we demonstrated for the first time that NF-kappaB plays a greater role in IL-15-induced cell proliferation than in IL-15- and IL-21-induced suppression of apoptosis.
Pelletier
Martin
M
Institut National de la Recherche Scientifique-Institut Armand-Frappier, Université du Québec, 245 Boulevard Hymus, Pointe-Claire H9R 1G6, Québec, Canada.
Girard
Denis
D
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D039481:CD11b Antigen / Q000096:biosynthesis* / Q000378:metabolism; D049109:Cell Proliferation; D018189:Immunomagnetic Separation; D019409:Interleukin-15 / Q000502:physiology*; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins / Q000502:physiology*; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D018123:Receptors, Interleukin / Q000096:biosynthesis; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D053655:Receptors, Interleukin-21; D013997:Time Factors; D000098546:Interleukin-21
D039481:CD11b Antigen; C508025:Il15ra protein, mouse; C508118:Il21r protein, mouse; D019409:Interleukin-15; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins; D052002:NF-kappa B p50 Subunit; D018123:Receptors, Interleukin; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D053655:Receptors, Interleukin-21; D000098546:Interleukin-21