IFN-β INHIBITS THE ABILITY OF T LYMPHOCYTES TO INDUCE TNF-α AND IL-1β PRODUCTION IN MONOCYTES UPON DIRECT CELL–CELL CONTACT

Jungo, Florence; Dayer, Jean‐Michel; Modoux, Christine; Hyka, Nevila; Burger, Danielle

doi:10.1006/cyto.2001.0884

Cited by 57 publications

(41 citation statements)

References 42 publications

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“…Like IFNβ, another immunomodulator used in MS therapy (27,28), GA induces sIL-1Ra production in isolated human monocytes, an activity reflected by the enhancement of sIL-1Ra levels in the blood of GA-treated MS patients and EAE mice (29). Thus, both GA and IFNβ, which display comparable therapeutic effects (30), act on sIL-1Ra levels that might be a common mode of action in MS treatment.…”

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confidence: 99%

Glatiramer acetate triggers PI3Kδ/Akt and MEK/ERK pathways to induce IL-1 receptor antagonist in human monocytes

Carpintero

Brandt

Gruaz

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Glatiramer acetate (GA), an immunomodulator used in multiple sclerosis (MS) therapy, induces the production of secreted IL-1 receptor antagonist (sIL-1Ra), a natural inhibitor of IL-1β, in human monocytes, and in turn enhances sIL-1Ra circulating levels in MS patients. GA is a mixture of peptides with random Glu, Lys, Ala, and Tyr sequences of high polarity and hydrophilic nature that is unlikely to cross the blood–brain barrier. In contrast, sIL-1Ra crosses the blood–brain barrier and, in turn, may mediate GA anti-inflammatory activities within the CNS by counteracting IL-1β activities. Here we identify intracellular signaling pathways induced by GA that control sIL-1Ra expression in human monocytes. By using kinase knockdown and specific inhibitors, we demonstrate that GA induces sIL-1Ra production via the activation of PI3Kδ, Akt, MEK1/2, and ERK1/2, demonstrating that both PI3Kδ/Akt and MEK/ERK pathways rule sIL-1Ra expression in human monocytes. The pathways act in parallel upstream glycogen synthase kinase-3α/β (GSK3α/β), the knockdown of which enhances sIL-1Ra production. Together, our findings demonstrate the existence of signal transduction triggered by GA, further highlighting the mechanisms of action of this drug in MS.

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confidence: 99%

Glatiramer acetate triggers PI3Kδ/Akt and MEK/ERK pathways to induce IL-1 receptor antagonist in human monocytes

Carpintero

Brandt

Gruaz

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Although several works reported a suppressive effect of type I IFNs in the TNFa production [30][31][32][33][34], other cellular studies suggested that this proposed inhibitory effect may be dependent on both cell type and inflammatory conditions. In this sense, it has been observed that IFNb diminishes in vitro TNFa production in T-cell contact-activated monocytes, while the same cytokine enhances TNFa production in LPS-activated monocytes [35].…”

Section: Discussionmentioning

confidence: 99%

Antimalarial drugs inhibit IFNα-enhanced TNFα and STAT4 expression in monocytes: Implication for systemic lupus erythematosus

López

Rodríguez‐Carrio

2014

Cytokine

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This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. Results: IFNa alone did not modify significantly TNFa production, but an increase was observed in stimulated PBMC. Further analyses showed that monocytes were the cellular population responsible for this effect. In addition, IFNa treatment increased STAT4 in stimulated monocytes, suggesting that TNFa upregulation could be mediated by STAT4. On the other hand, the analysis of the antimalarial effect showed that chloroquine was able to inhibit in vitro the expression of TNFa and STAT4 enhanced by IFNa. In antimalarial-treated SLE patients, however, only those with high IFNa serum levels presented lower expression of STAT4. Conclusions: IFNa treatment enhances the induction of TNFa and STAT4 in stimulated monocytes, an effect inhibited in vitro by chloroquine treatment. However, the consequence of antimalarial treatment on SLE patients could be different depending on their IFNa serum levels.

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“…HUT-78 cells were cultured and activated by PHA (1 µg/ml) and PMA (5 ng/ml) in RPMI 1640 medium supplemented with 10% heat activated FCS, 50 µg/ml streptomycin, 50 U/ml penicillin, 2 mM glutamine (complete RPMI medium) in a 5% CO 2 -air humidified atmosphere at 37°C as described elsewhere [34]. Plasma membranes of stimulated HUT-78 cells were isolated and solubilized with CHAPS to obtain membrane CHAPS extract (CE sHUT ) as previously described [35]. The capacity of CE sHUT to activate human monocytes was equivalent to living HUT-78 cells or primary human T lymphocytes (i.e., in cocultures), fixed T cells, or isolated membranes as previously determined [34][35][36].…”

Section: T Cells and Preparation Of T Cell Plasma Membranesmentioning

confidence: 99%

Interleukin-1β production in human monocytes/macrophages is differentially regulated by MEK1 upon sterile and infectious inflammatory conditions

Carpintero¹,

Brandt²,

Gruaz³

et al. 2014

SOJ Immunol

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IFN-β INHIBITS THE ABILITY OF T LYMPHOCYTES TO INDUCE TNF-α AND IL-1β PRODUCTION IN MONOCYTES UPON DIRECT CELL–CELL CONTACT

Cited by 57 publications

References 42 publications

Glatiramer acetate triggers PI3Kδ/Akt and MEK/ERK pathways to induce IL-1 receptor antagonist in human monocytes

Glatiramer acetate triggers PI3Kδ/Akt and MEK/ERK pathways to induce IL-1 receptor antagonist in human monocytes

Antimalarial drugs inhibit IFNα-enhanced TNFα and STAT4 expression in monocytes: Implication for systemic lupus erythematosus

Interleukin-1β production in human monocytes/macrophages is differentially regulated by MEK1 upon sterile and infectious inflammatory conditions

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