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 / Conti, P.; Feliciani, C.; And, Barbacane; R. C., and Panara; M. R., and Reale; M., and Placido; F. C., and Sauder; D. N., and Dempsey; R. A., and Amerio. - 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

Feliciani C.
Membro del Collaboration Group
;
1992-01-01

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.
1992
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 / Conti, P.; Feliciani, C.; And, Barbacane; R. C., and Panara; M. R., and Reale; M., and Placido; F. C., and Sauder; D. N., and Dempsey; R. A., and Amerio. - In: IMMUNOLOGY. - ISSN 0019-2805. - 77:2(1992), pp. 245-250.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2862909
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 24
  • ???jsp.display-item.citation.isi??? ND
social impact