Glucocorticoid up-regulation of high-affinity interleukin 6 receptors on human epithelial cells.

Snyers, Luc; Wit, L. De

doi:10.1073/pnas.87.7.2838

Cited by 131 publications

(66 citation statements)

References 42 publications

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“…When SFs were pretreated with the glucocorticoid dexamethasone (dex), addition of IL-6 alone activated STAT DNA binding (Fig. 1B), consistent with previous results that cell surface expression of IL-6R␣ is induced by glucocorticoids (41). The induction of cellular responsiveness to IL-6 by the potent immunosuppressive agent dex is consistent with an anti-inflammatory action of IL-6 on SFs.…”

Section: Activation Of the Jak-stat Signal Transduction Pathway By Ilsupporting

confidence: 77%

Cross-Talk Between IL-1 and IL-6 Signaling Pathways in Rheumatoid Arthritis Synovial Fibroblasts

Deon

Ahmed

Tai

et al. 2001

The Journal of Immunology

102

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The balance between pro- and anti-inflammatory cytokines plays an important role in determining the severity of inflammation in rheumatoid arthritis (RA). Antagonism between opposing cytokines at the level of signal transduction plays an important role in many other systems. We have begun to explore the possible contribution of signal transduction cross-talk to cytokine balance in RA by examining the effects of IL-1, a proinflammatory cytokine, on the signaling and action of IL-6, a pleiotropic cytokine that has both pro- and anti-inflammatory actions, in RA synovial fibroblasts. Pretreatment with IL-1 suppressed Janus kinase-STAT signaling by IL-6, modified patterns of gene activation, and blocked IL-6 induction of tissue inhibitor of metalloproteases 1 expression. These results suggest that proinflammatory cytokines may contribute to pathogenesis by modulating or blocking signal transduction by pleiotropic or anti-inflammatory cytokines. The mechanism of inhibition did not require de novo gene activation and did not depend upon tyrosine phosphatase activity, but, instead, was dependent on the p38 stress kinase. These results identify a molecular basis for IL-1 and IL-6 cross-talk in RA synoviocytes and suggest that, in addition to levels of cytokine expression, modulation of signal transduction also plays a role in regulating cytokine balance in RA.

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Section: Activation Of the Jak-stat Signal Transduction Pathway By Ilsupporting

confidence: 77%

Cross-Talk Between IL-1 and IL-6 Signaling Pathways in Rheumatoid Arthritis Synovial Fibroblasts

Deon

Ahmed

Tai

et al. 2001

The Journal of Immunology

102

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“…In various inflammatory states elevated glucocorticoid levels are observed. We and others have described that gpg0-mgNA as well as the functional protein is induced by glucocorticoids and not by IL-6 [18,19]. In the present study, evidence is presented that IL-6 and in parti.…”

Section: Discussionsupporting

confidence: 61%

“…Therefore, the regulation of the hepatic 80 kDa-IL-6-R subunit has been studied. It was found that glucocorticoids, but not IL-6 up-regulated mRNA as well as functional protein expression of gp80 [18,19]. Thus far, nothing is known about the regulation of the second subunit of the hepatic IL-6-R (gp130).…”

Section: Il-6 Is a Multifunctional Eytokine Involved Inmentioning

confidence: 99%

Up‐regulation of the interleukin‐6‐signal transducing protein (gp130) by interleukin‐6 and dexamethasone in HepG2 cells

et al. 1992

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Tile hepatic IL-6-recaptor is composed of an 80 kDa IL-6-binding protein and a 130 kDa polypeptide (gp130) believod to be involved in signal transduction. Previous experiments have shown that the 80 kDa IL-6.receptor is up-regulated by glucocortieoids, but not by IL-6. Here we demonstrate that IL-6 together with the synthetic 81ucocorticold dexamethasone induces the expression ofmRNA for gpl3O approximately S-fold in HepG2 cells. The induction was dose-and time-delYendent. Dexamethasone alone, interferon-7, IL-lrr and IL-Ip had no effect. A possible role for the regulation of the IL-6-signal transducing protein gpl30 in various inflammatory states is proposed.

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“…In this regard, pretreatment of humans with cortisol prior to endotoxin increased circulating concentrations of TNFα and IL-6 (46). Furthermore, glucocorticoids act synergistically with either cytokines or endotoxin to increase other diverse inflammatory mediators, such toll-like receptor-2 mRNA and protein (47), IL-6 receptor number (48), and under some conditions the acute-phase protein response (49).…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoids and TNFα Interact Cooperatively to Mediate Sepsis-Induced Leucine Resistance in Skeletal Muscle

Lang

Frost

2006

Mol Med

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Sepsis blunts the ability of nutrient signaling by leucine to stimulate skeletal muscle protein synthesis by impairing translation initiation. The present study tested the hypothesis that overproduction of either tumor necrosis factor (TNF)-α or glucocorticoids mediate the sepsis-induced leucine resistance. Prior to producing peritonitis, rats received either vehicle, TNF binding protein (TNF BP ) to inhibit endogenous TNFα action, and/or the glucocorticoid receptor antagonist RU486. Leucine was orally administered to all rats 24 h thereafter and the gastrocnemius removed 20 min later to assess protein synthesis and signaling components important in controlling peptide-chain initiation. Muscle protein synthesis was 65% lower in septic rats administered leucine than in leucinetreated control animals. This reduction was not prevented by either TNF BP or RU486 alone, but was completely reversed by the combination. This sepsis-induced leucine resistance was associated with an 80% reduction in the amount of active eIF4E·eIF4G complex, a 5-fold increase in the formation of the inactive eIF4E·4E-BP1 complex as well as markedly reduced (at least 70%) phosphorylation of 4E-BP1, eIF4G, S6K1, S6, and mTOR. Pretreatment of septic rats with either TNF BP or RU486 individually only nominally improved the leucine action as assessed by the above-mentioned endpoints. In contrast, when TNF BP and RU486 were co-administered, the ability of sepsis to impair the leucine-stimulated phosphorylation of 4E-BP1, eIF4G, S6K1, and S6 as well as the redistribution of eIF4E was essentially prevented. No differences in the total amount or phosphorylation of eIF2α and eIF2Bε were detected between the different groups, and changes could not be attributed to differences in the prevailing plasma concentration of insulin or leucine. Our data demonstrate the sepsis-induced leucine resistance in skeletal muscle results from the cooperative interaction of both TNFα and glucocorticoids.

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Glucocorticoid up-regulation of high-affinity interleukin 6 receptors on human epithelial cells.

Cited by 131 publications

References 42 publications

Cross-Talk Between IL-1 and IL-6 Signaling Pathways in Rheumatoid Arthritis Synovial Fibroblasts

Cross-Talk Between IL-1 and IL-6 Signaling Pathways in Rheumatoid Arthritis Synovial Fibroblasts

Up‐regulation of the interleukin‐6‐signal transducing protein (gp130) by interleukin‐6 and dexamethasone in HepG2 cells

Glucocorticoids and TNFα Interact Cooperatively to Mediate Sepsis-Induced Leucine Resistance in Skeletal Muscle

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