FEBS Letters | |
Human recombinant interleukin‐1 receptor antagonist inhibits lymphocyte blastogenesis induced by concanavalin A Restorative effect of hrIL‐1 | |
Panara, Maria R.3  Reale, Marcella1  Barbacane, Renato C.1  Conti, Pio1  Dempsey, Roy A.2  Bongrazio, Mauro3  | |
[1] Immunology Division, Institute of Experimental Medicine, University of Chieti, 66100 Chieti, Italy;Cytokine Research Laboratory, Endogen, Inc., Boston, MA 02111, USA;Institute of Normal and Pathologic Cytomorphology, CNR, University of Chieti, 66100 Chieti, Italy | |
关键词: Interleukin-1 receptor antagonist; Concanavalin A; Lymphocyte; Blastogenesis; Interleukin; T-cell; hrIL-1ra; human recombinant interleukin-1 receptor antagonist; hrIL-1; human recombinant interleukin-1; IL-2; interleukin-2; Con A; concanavalin A; PBMC; peripheral blood mononuclear cells; 3H-TdR; [methyl-3H]thymidine; | |
DOI : 10.1016/0014-5793(91)80959-7 | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
Interleukin-1 (IL-1), mainly produced by monocyte-macrophages, is a polypeptide cytokine with pleiotropic biological effects. IL-1 plays an important role in mediating immune response and inflammation. Recently a natural inhibitor to IL-1 has been discovered, interleukin-1 receptor antagonist (IL-1ra), produced by human monocytes cultured on adherent IgG which binds to the IL-1 receptors. In our study we found that the pretreatment of cells with serial dilutions of IL-1ra (250 ng/ml−2.5 pg/ml) inhibits, in a dose-dependent manner, lymphocyte DNA synthesis stimulated with Con A (10 μg/ml). IL-1ra did not have any effect on resting peripheral blood mononuclear cells (PBMC). Time course experiments show that IL-1ra at 250 ng/ml has its maximum inhibitory effect on lymphocyte blastogenesis when cells are pretreated 2 h before Con A. No effect was found when hrIL-1ra was added after Con A. Moreover, hrIL-1ra also inhibits the enhancing effects of exogenous hrIL-1 (400, 200, 100 and 50 ng/ml) on lymphocytes stimulated with Con A; while when hrIL-1ra was used on cells treated with only Con A, the inhibition was more pronounced. When PBMC were removed from monocytes, by adherence, the Con A-treated lymphocytes were not influenced by 2 h pretreatment of hrIL-1ra; while a strong inhibition was found when exogenous hrIL-1 was added at different concentrations. In addition, hrIL-1ra also inhibits the enhancing effect of hrIL-2 on lymphocyte DNA synthesis. In another set of experiments PBMC were pretreated with hrIL-1ra (250 ng/ml) for 2 h and then added LPs (10 ng/ml) and IL-1α generation was determined using ELISA. In these experiments IL-1ra completely abolished the generation of IL-1α. These data suggest that hrIL-1ra exhibits a dose—response inhibition of lymphocyte blastogenesis induced by Con A, probably through the down-regulation of IL-1 synthesis necessary as an early signal for T-cell activation and IL-2 production.
【 授权许可】
Unknown
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