+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

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



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



Immunology 77(2): 245-250



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-1 beta 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-1 receptor antagonist on IL-1 we have studied the influence of rhIL-1Ra on IL-1 transcription and translation. In this report we show that IL-1 beta 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-1 beta 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-1 alpha and IL-1 beta secretion in human PBMC, as measured by ELISA method. In fact, herein we show that LPS activates human PBMC to secrete IL-1 beta and IL-1 alpha, 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-1 alpha to stimulate the secretion of IL-1 beta in human PBMC. This activation, carried out overnight, also provoked the release of IL-1 beta 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-1 beta stimulated by IL-1 alpha, may contribute to therapeutic effects in inflammatory diseases such as rheumatoid arthritis and other autoimmune diseases.(ABSTRACT TRUNCATED AT 400 WORDS)

(PDF emailed within 1 workday: $29.90)

Accession: 040446532

Download citation: RISBibTeXText

PMID: 1427978


Related references

Interferon-beta not only inhibits interleukin-1beta and tumor necrosis factor-alpha but stimulates interleukin-1 receptor antagonist production in human peripheral blood mononuclear cells. European Cytokine Network 8(4): 345-349, 1998

Fibrin matrices stimulate procoagulant activity, promote the expression of interleukin-1-beta, and suppress interleukin-1 receptor antagonist in human peripheral blood mononuclear cells. Clinical Research 41(2): 282A, 1993

Interleukin 2 il 2 stimulates the production of interleukin 1 beta il 1 beta interleukin 1 alpha il 1 alpha and tumor necrosis factor alpha tnf alpha from human peripheral blood mononuclear cells pbmc. Journal of Leukocyte Biology 42(5): 545, 1987

Interleukin-1 beta, interleukin-1 receptor antagonist mRNA expression of peripheral blood mononuclear cells (PBMC) in idiopathic nephrotic syndrome (INS) detected by biotin-labelled probe in situ hybridization. Zhonghua Yi Xue Za Zhi 75(3): 152-4, 190, 1995

Inhibition of Interleukin-1 (Alpha and Beta), Interleukin-2 Secretion and Surface Expression of Interleukin-2 Receptor (IL-2R) by a Novel Cytokine Interleukin-1 Receptor Antagonist (IL-lra). Scandinavian Journal of Immunology 36(1): 27-34, 1992

Inhibition of interleukin-1 (alpha and beta), interleukin-2 secretion and surface expression of interleukin-2 receptor (IL-2R) by a novel cytokine interleukin-1 receptor antagonist (IL-1ra). Scandinavian Journal of Immunology 36(1): 27-33, 1992

Expression of interleukin-1 alpha, interleukin-1 beta, and an interleukin-1 receptor antagonist in human retinal pigment epithelial cells. Experimental Eye Research 55(2): 325-335, 1992

Human recombinant interleukin-1 receptor antagonist blocks bone resorption induced by interleukin-1 beta but not interleukin-1 alpha. Calcified Tissue International 55(1): 12-15, 1994

Tumor necrosis factor alpha tnf alpha interleukin 1 beta il 1 beta and interleukin 6 il 6 synthesis in human peripheral blood mononuclear cells pbmnc stimulated in vitro and in vivo by proteolytic enzymes. European Journal of Cancer 27(SUPPL 3): S75, 1991

Immunoglobulin D enhances the release of tumour necrosis factor-alpha, and interleukin-1-beta as well as interleukin-1 receptor antagonist from human mononuclear cells. Immunology 88(3): 355-362, 1996

Production of interleukin-1 receptor antagonist and interleukin-1 beta by peripheral blood mononuclear cells is differentially regulated. Blood 78(5): 1275-1281, 1991

Differential regulation of the interleukin receptor antagonist and interleukin 1 beta production by peripheral blood mononuclear cells. Clinical Research 39(2): 288A, 1991

Dialysis-induced alterations in interleukin receptor antagonist and interleukin-1-beta production by peripheral-blood mononuclear cells. Blood Purification 10(2): 102-103, 1992

Influence of dialysis membranes on interleukin-1 beta and interleukin-1 receptor antagonist production by peripheral blood mononuclear cells. Artificial Organs 21(4): 265-271, 1997

Human mesangial cells synthesize interleukin 1 alpha but not interleukin 1 beta, interleukin 1 receptor antagonist, or tumour necrosis factor. Nephrology, Dialysis, Transplantation 7(10): 997-1001, 1992