The transcription and translation of interleukin-1 (IL-1) may have a pleiotropic effect on the immune system and inflammatory diseases. Recently it has been reported that human monocytes not only produce IL-1 but also induce, with adherent IgG, the secretion of an IL-1 receptor antagonist (IL-1Ra), which can play an essential in vivo and in vitro role in the regulation of IL-1 activity. Recombinant human (rh) IL-1Ra is structurally similar to IL-1β but with no IL-1-like activity, and specifically binds to the IL-1 receptor. To more fully evaluate and clarify the inhibitory effect of rhIL-1receptor antagonist on IL-1 we have studied the influence of rhIL-1 Ra on IL-1 transcription and translation. In this report we show that IL-1β mRNA from peripheral blood mononuclear cells (PBMC) is strongly inhibited (66%) when rhIL-1Ra (250 ng/ml) was added to cultured cells activated with lipopolysaccharide (LPS) (100 ng/ml) for 4 hr, determined with the slot blot analysis. The addition of exogenous rhIL-1β to the cell culture diminished the inhibitory effect (44%). Moreover, we report that the block of IL-1 mRNA transcription consequently leads to the inhibition of IL-1α and IL-1β secretion in human PBMC, as measured by ELISA method. In fact, herein we show that LPS activates human PBMC to secrete IL-1β and IL-1α, an effect inhibited, in a dose-dependent fashion by rhIL-1Ra (0.025-250 ng/ml) in an overnight incubation. Since IL-1 is a strong inducer of IL-1 synthesis in vivo and in vitro, in our study we used rh IL-1α to stimulate the secretion of IL-1β in human PBMC. This activation, carried out overnight, also provoked the release of IL-1β in a dose-dependent manner, which was strongly inhibited by rhIL-1Ra used at different concentrations (0.025-250 ng/ml). The inhibitory effect exerted by IL-1Ra on human PBMC IL-1 mRNA transcription and the down-regulation of secretion of IL-1β stimulated by IL-1α, may contribute to therapeutic effects in inflammatory diseases such as rheumatoid arthritis and other autoimmune diseases. We conclude that the suppression of IL-1 mRNA occurring in an early stage consequently provokes an inhibition of post-transcriptional formation of IL-1, and may therefore prove that IL-1Ra is probably part of a physiological system for regulating normal and pathological activities of IL-1 and its inducers.

Inhibition of interleukin-1β mRNA expression and interleukin-1α and β secretion by a specific human recombinant interleukin-1 receptor antagonist in human peripheral blood mononuclear cells / P., Conti; Feliciani, C.; and Barbacane, C.; and Panara, R. C.; and Reale, M. R.; and Placido, M.; and Sauder, F. C.; and Dempsey, D. N.; and Amerio, R. A.. - In: IMMUNOLOGY. - ISSN 0019-2805. - 77:2(1992), pp. 245-250.

Inhibition of interleukin-1β mRNA expression and interleukin-1α and β secretion by a specific human recombinant interleukin-1 receptor antagonist in human peripheral blood mononuclear cells

c. Feliciani
Data Curation
;
1992

Abstract

The transcription and translation of interleukin-1 (IL-1) may have a pleiotropic effect on the immune system and inflammatory diseases. Recently it has been reported that human monocytes not only produce IL-1 but also induce, with adherent IgG, the secretion of an IL-1 receptor antagonist (IL-1Ra), which can play an essential in vivo and in vitro role in the regulation of IL-1 activity. Recombinant human (rh) IL-1Ra is structurally similar to IL-1β but with no IL-1-like activity, and specifically binds to the IL-1 receptor. To more fully evaluate and clarify the inhibitory effect of rhIL-1receptor antagonist on IL-1 we have studied the influence of rhIL-1 Ra on IL-1 transcription and translation. In this report we show that IL-1β mRNA from peripheral blood mononuclear cells (PBMC) is strongly inhibited (66%) when rhIL-1Ra (250 ng/ml) was added to cultured cells activated with lipopolysaccharide (LPS) (100 ng/ml) for 4 hr, determined with the slot blot analysis. The addition of exogenous rhIL-1β to the cell culture diminished the inhibitory effect (44%). Moreover, we report that the block of IL-1 mRNA transcription consequently leads to the inhibition of IL-1α and IL-1β secretion in human PBMC, as measured by ELISA method. In fact, herein we show that LPS activates human PBMC to secrete IL-1β and IL-1α, an effect inhibited, in a dose-dependent fashion by rhIL-1Ra (0.025-250 ng/ml) in an overnight incubation. Since IL-1 is a strong inducer of IL-1 synthesis in vivo and in vitro, in our study we used rh IL-1α to stimulate the secretion of IL-1β in human PBMC. This activation, carried out overnight, also provoked the release of IL-1β in a dose-dependent manner, which was strongly inhibited by rhIL-1Ra used at different concentrations (0.025-250 ng/ml). The inhibitory effect exerted by IL-1Ra on human PBMC IL-1 mRNA transcription and the down-regulation of secretion of IL-1β stimulated by IL-1α, may contribute to therapeutic effects in inflammatory diseases such as rheumatoid arthritis and other autoimmune diseases. We conclude that the suppression of IL-1 mRNA occurring in an early stage consequently provokes an inhibition of post-transcriptional formation of IL-1, and may therefore prove that IL-1Ra is probably part of a physiological system for regulating normal and pathological activities of IL-1 and its inducers.
Inhibition of interleukin-1β mRNA expression and interleukin-1α and β secretion by a specific human recombinant interleukin-1 receptor antagonist in human peripheral blood mononuclear cells / P., Conti; Feliciani, C.; and Barbacane, C.; and Panara, R. C.; and Reale, M. R.; and Placido, M.; and Sauder, F. C.; and Dempsey, D. N.; and Amerio, R. A.. - In: IMMUNOLOGY. - ISSN 0019-2805. - 77:2(1992), pp. 245-250.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11381/2866504
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