Biological properties of recombinant human monocyte-derived interleukin 1 receptor antagonist.

Arend, William P.; Welgus, Howard G.; Thompson, Robert C.; Eisenberg, Stephen P.

doi:10.1172/jci114622

Cited by 541 publications

(248 citation statements)

References 22 publications

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“…Our daia support the study produced by Arend et ai, who found inhibition by hrlL-IRa of another arachidonic acid metabolite, a cyciooxygenase product, PGE2 [22]. The mechanism and the molecular changes that occur in the human monocyte.…”

Section: Discussionsupporting

confidence: 89%

“…wt 22000 (glycosylated form) and 17000 (non-glycosylaled form), could theoretically interfere with any one of these steps [19,20]. IL-!Ra is secreted by human monocyles and is structurally similar to IL-1/f (26' Vi> amino acid homology) and IL-la (19% homology), but with no iL-l-like aetivity [21][22]. IL-lRa is a natural inhibitor of IL-I and is capable of inhibiting eyelooxygenase and down-regulating DNA synthesis in mitogen-stimulated lymphoeytes.…”

Section: Introdlfctionmentioning

confidence: 99%

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Human recombinant IL-1 receptor antagonist (IL-IRa) inhibits leukotriene B4 generation from human monocyte suspensions stimulated by lipopolysaccharide (LPS)

Conti

Panara

Barbacane

et al. 1993

Clinical and Experimental Immunology

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SUMMARYThe efiect of human recombinant IL-1 receptor antagonist (hrlL-lRa) on leukotriene B4 (LTB4) release was investigated in activated human monocyte cultures. To stimulate LTB4 generation, LPS was used as an agonist. Detection was performed with the highly sensitive radioimmunoassay method. The cells were treated with scalar concentrations using LPS at I -IOOO ng/ml for different periods or lime. The greater LTB4 stimulaiion was found at LPS 100 ng/ml for 18 h incubation time. Preincubation of monocytes with cytochalasin B (CB) (5 ^ig/ml) for 15 min augmented the release of LTB4 when LPS was used. A dose-dependent inhibition was found when human monocytes were pretreated for 10 min with hrlL-l Ra at dilTerent concentrations (0-25-25O ng/ml) and then treated with LPS 100 ng/ml for 18 h. Maximum inhibition was observed at the highest concentration of hriLlRa (250 ng/ml), Macrophages treated with a non-selective 5-lipoxygenase inhibitor, nordihydroguaiarclic acid (NDGA). used at 10 fm, added 15 min before LPS 100 ng/ml. produee a dosedependent inhibition of LTB4, Cells pretreated with araehidonic acid, at various concentrations (U) " 10 'M)for 10 min and then treated with LPS 100 ng/ml for 18 h, were also inhibited in a dosedependent manner by hrlL-l Ra in their production of LTB4. The inhibition of LTB4 release by hriLIRa. in LPS-stimulatcd human monocytes. may suggest an important modulatory role for this new cytokine (monokine) in inflammation and immunity and may hold future therapeutic implications for disea.ses involving LTB4 as a mediator. [9][10][11][12]. in general the release ofeicosanoids is associated with many pathophysiological phenomena such as hypotension, thrombocytopenia. capillary leak syndrome. Icukopenia and fever, all factors involved in the shock syndrome which occurs, for example, in in viro cytokine therapies [13][14][15], Araehidonic acid. released from activated macrophages. is the precursor of eyelooxygenase and lipoxygenasc compounds. In particular. lunnan macrophages oxidatively metabolize endogenous ara-C'orrcspoiidoncc: Dr Pit* Conli. Immunology Divisitiii. Instilute of Experimental Medicine. University of Cliieti Medical School. Via dei Vestini. 66100 Chieti, Italy. chidonic add to teukotriene B4 {LTB4) (5S,I2R-dihydroxy-6. l4-cis-8. 10-trans eicosatetraenoic acid) by the specific lipoxygenation pathway. Macrophages cultured in vitro release LTB4 in response lo stimulation with LPS [I6|. Macrophages release an impressive array of biologically active molecules, among which are molecules with the ability to direct the stimulation of araehidonic acid products. LTB4 is one human macrophage product with numerous effects on a variety of leucocytes, which has a potent chemokinetic and chcmotaclic activity, induction of aggregation, and has a profound ability to modulate macrophage functions [16][17][18]. The receptor-stimulated activation mechanism is poorly understood. Following LPS stimulation of mononuclear phagocytes a number of events occur which are related to the release of LTB...

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Section: Discussionsupporting

confidence: 89%

Section: Introdlfctionmentioning

confidence: 99%

Human recombinant IL-1 receptor antagonist (IL-IRa) inhibits leukotriene B4 generation from human monocyte suspensions stimulated by lipopolysaccharide (LPS)

Conti

Panara

Barbacane

et al. 1993

Clinical and Experimental Immunology

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“…However, it remains unclear whether sIL-1ra can directly regulate the level of ICE gene expression before it is secreted or some other co-factors play a crucial role in ICE regulation at the transcription level of sIL-1ra, and the further study will be needed to clarify this mechanism. It is well known that a 10-to 100-fold molar excess of IL-1ra is often required to inhibit IL-1 activity (Arend et al, 1990). In the present study, we found that IL-1ra/IL-1β ratios in the supernatants were less than 10 in , while those were more than 10 in KU-1 and KU-2.…”

Section: Figuresupporting

confidence: 50%

Overexpression of IL-1ra gene up-regulates interleukin-1β converting enzyme (ICE) gene expression: Possible mechanism underlying IL-1β-resistance of cancer cells

et al. 1999

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Ala-Asp-CHO (YVAD-CHO) blocked IL-1β-induced growth inhibition in KU-1 and KU-2. Overexpression of the secretory type IL-1ra with adenovirus vector (AxIL-1ra) enhanced ICE gene expression, while exogenous IL-1ra (100 ng ml -1 ) did not enhance it. Furthermore, AxIL-1ra treatment promoted endogenous IL-1β secretion and induced significant growth inhibition and apoptotic cell death on . Treatment with either IL-1ra (100 ng ml -1 ), IL-1β antibody (100 µg ml -1 ), or YVAD-CHO blocked AxIL-1ra-induced cell death in . These results suggest that IL-1β-sensitivity depends on the level of ICE gene expression, which is regulated by the level of endogenous sIL-1ra expression. This is a first report on the intracellular function of sIL-1ra and these findings may provide key insights into the mechanism underlying the viability of cancer cells.

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“…These doses of individual factors were within the range between effective dose 75 and effective dose 100 of their proper effects on chondrocytes, according to dose-response curves in the previous reports (11,12,15,16,(21)(22)(23)(24)(25)(26)(27)(28) cells in 5 l of 0.8% atelocollagen gel) were cultured in Dulbecco's modified Eagle's medium/F-12 containing the combinations for 2 weeks, and the GAG accumulation was measured as described below. Parameter estimates of the GAG accumulation by one factor or two were calculated from the F values that represent the effects of the individual factors and the interaction terms of two factors by the analysis of variance using the software above.…”

Section: Methodsmentioning

confidence: 57%

Optimal Combination of Soluble Factors for Tissue Engineering of Permanent Cartilage from Cultured Human Chondrocytes

Liu

Kawaguchi

Ogasawara

et al. 2007

Journal of Biological Chemistry

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Since permanent cartilage has poor self-regenerative capacity, its regeneration from autologous human chondrocytes using a tissue engineering technique may greatly benefit the treatment of various skeletal disorders. However, the conventional autologous chondrocyte implantation is insufficient both in quantity and in quality due to two major limitations: dedifferentiation during a long term culture for multiplication and hypertrophic differentiation by stimulation for the redifferentiation. To overcome the limitations, this study attempted to determine the optimal combination in primary human chondrocyte cultures under a serum-free condition, from among 12 putative chondrocyte regulators. From the exhaustive 2 12 ‫؍‬ 4,096 combinations, 256 were selected by fractional factorial design, and bone morphogenetic protein-2 and insulin (BI) were statistically determined to be the most effective combination causing redifferentiation of the dedifferentiated cells after repeated passaging. We further found that the addition of triiodothyronine (T3) prevented the BI-induced hypertrophic differentiation of redifferentiated chondrocytes via the suppression of Akt signaling. The implant formed by the human chondrocytes cultured in atelocollagen and poly(L-latic acid) scaffold under the BI ؉ T3 stimulation consisted of sufficient hyaline cartilage with mechanical properties comparable with native cartilage after transplantation in nude mice, indicating that BI ؉ T3 is the optimal combination to regenerate a clinically practical permanent cartilage from autologous chondrocytes.

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Biological properties of recombinant human monocyte-derived interleukin 1 receptor antagonist.

Cited by 541 publications

References 22 publications

Human recombinant IL-1 receptor antagonist (IL-IRa) inhibits leukotriene B4 generation from human monocyte suspensions stimulated by lipopolysaccharide (LPS)

Human recombinant IL-1 receptor antagonist (IL-IRa) inhibits leukotriene B4 generation from human monocyte suspensions stimulated by lipopolysaccharide (LPS)

Overexpression of IL-1ra gene up-regulates interleukin-1β converting enzyme (ICE) gene expression: Possible mechanism underlying IL-1β-resistance of cancer cells

Optimal Combination of Soluble Factors for Tissue Engineering of Permanent Cartilage from Cultured Human Chondrocytes

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