Interleukin-1

Stylianou, Eleni; Saklatvala, Jeremy

doi:10.1016/s1357-2725(98)00081-8

Cited by 202 publications

(149 citation statements)

References 16 publications

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“…The promoter regions of genes encoding IL-1β, TNF-α and iNOS contain CREB binding sites (Stylianou and Saklatvala 1998;Galea and Feinstein, 1999;Tsai et al, 2000). Therefore, PKA may regulate IL-1β, TNF-α and iNOS expression via CREB phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

“…Plasm inogen regulates DNA binding activities of CREB and NF-κB via protein kinase A cAMP response element (CRE) and NF-κB binding sites exist in the promoter regions of genes encoding IL-1β, TNF-α and iNOS (Collart et al, 1990;Hiscott et al, 1993;Wong et al, 1996;Kinugawa et al, 1997;Stylianou and Saklatvala, 1998;Tsai et al, 2000;Chang et al, 2004). Furthermore, plasminogen increases the DNA binding activities of CRE binding protein (CREB) and NF-κB (Min et al, 2003).…”

Section: R Esultsmentioning

confidence: 99%

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Protein kinase A mediates microglial activation induced by plasminogen and gangliosides

Min

Yang²,

Jou³

et al. 2004

Exp Mol Med

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Section: Discussionmentioning

confidence: 99%

Section: R Esultsmentioning

confidence: 99%

Protein kinase A mediates microglial activation induced by plasminogen and gangliosides

Min

Yang²,

Jou³

et al. 2004

Exp Mol Med

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“…Comparable results were obtained in additional cell assays (not shown), demonstrating that this effect is not unique to a particular cell line or assay system. IL-1␤ has been shown to activate a number of specific protein kinases, including the NF B-inducing kinase (NIK) and three distinct mitogen-activated protein (MAP) kinase cascades (37). To determine whether binding by XOMA 052 might have differential effects on signaling through the different pathways, we measured phosphorylation of JNK, ERK 1/2, and p38, as well as total I B levels, by increasing concentrations of IL-1␤ in the presence and absence of excess XOMA 052 (Fig.…”

Section: Interaction By Sprmentioning

confidence: 99%

Kinetic Approach to Pathway Attenuation Using XOMA 052, a Regulatory Therapeutic Antibody That Modulates Interleukin-1β Activity

Roell

Issafras

Bauer³

et al. 2010

Journal of Biological Chemistry

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Many therapeutic antibodies act as antagonists to competitively block cellular signaling pathways. We describe here an approach for the therapeutic use of monoclonal antibodies based on context-dependent attenuation to reduce pathologically high activity while allowing homeostatic signaling in biologically important pathways. Such attenuation is achieved by modulating the kinetics of a ligand binding to its various receptors and regulatory proteins rather than by complete blockade of signaling pathways. The anti-interleukin-1␤ (IL-1␤) antibody XOMA 052 is a potent inhibitor of IL-1␤ activity that reduces the affinity of IL-1␤ for its signaling receptor and co-receptor but not for its decoy and soluble inhibitory receptors. This mechanism shifts the effective dose response of the cytokine so that the potency of IL-1␤ bound by XOMA 052 is 20 -100-fold lower than that of IL-1␤ in the absence of antibody in a variety of in vitro cell-based assays. We propose that by decreasing potency of IL-1␤ while allowing binding to its clearance and inhibitory receptors, XOMA 052 treatment will attenuate IL-1␤ activity in concert with endogenous regulatory mechanisms. Furthermore, the ability to bind the decoy receptor may reduce the potential for accumulation of antibody⅐target complexes. Regulatory antibodies like XOMA 052, which selectively modulate signaling pathways, may represent a new mechanistic class of therapeutic antibodies.

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“…This suggests that the inhibitory action of thalidomide on NF-B binding lies downstream of the cytokine-receptor interaction and recruitment of associated factors but upstream of the induction of NF-B nuclear translocation. Both TNF␣ and IL-1␤ signal NF-B activation through the induction of IKK (30,(45)(46)(47)(48). IKK activation results in the phosphorylation of IB␣ on serine residues 32 and 36, which ultimately leads to the degradation of this inhibitor (49 -52).…”

Section: Inhibition Of Il-8 Gene Expression In Endothelialmentioning

confidence: 99%

Inhibition of NF-κB Activity by Thalidomide through Suppression of IκB Kinase Activity

Keifer

Guttridge

Ashburner

et al. 2001

Journal of Biological Chemistry

451

255

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The sedative and anti-nausea drug thalidomide, which causes birth defects in humans, has been shown to have both anti-inflammatory and anti-oncogenic properties. The anti-inflammatory effect of thalidomide is associated with suppression of cytokine expression and the anti-oncogenic effect with inhibition of angiogenesis. It is presently unclear whether the teratogenic properties of thalidomide are connected in any way to the beneficial, anti-disease characteristics of this drug. The transcription factor NF-B has been shown to be a key regulator of inflammatory genes such as tumor necrosis factor-␣ and interleukin-8. Inhibition of NF-B is associated with reduced inflammation in animal models, such as those for rheumatoid arthritis. We show here that thalidomide can block NF-B activation through a mechanism that involves the inhibition of activity of the IB kinase. Consistent with the observed inhibition of NF-B, thalidomide blocked the cytokine-induced expression of NF-B-regulated genes such as those encoding interleukin-8, TRAF1, and c-IAP2. These data indicate that the therapeutic potential for thalidomide may be based on its ability to block NF-B activation through suppression of IB kinase activity.

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Interleukin-1

Cited by 202 publications

References 16 publications

Protein kinase A mediates microglial activation induced by plasminogen and gangliosides

Protein kinase A mediates microglial activation induced by plasminogen and gangliosides

Kinetic Approach to Pathway Attenuation Using XOMA 052, a Regulatory Therapeutic Antibody That Modulates Interleukin-1β Activity

Inhibition of NF-κB Activity by Thalidomide through Suppression of IκB Kinase Activity

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