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This article is part of the supplement: 25th European Workshop for Rheumatology Research

Poster presentation

Different molecules at the surface of stimulated T cells induce IL-1beta, tumour necrosis factor and IL-1RA in human monocytes

D Burger, N Molnarfi, L Gruaz and JM Dayer

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Division of Immunology and Allergy, Clinical Immunology Unit, Faculty of Medicine, University Hospital, Geneva, Switzerland

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Citation and License

Arthritis Research & Therapy 2005, 7(Suppl 1):P113  doi:10.1186/ar1634


The electronic version of this article is the complete one and can be found online at:


Received:11 January 2005
Published:17 February 2005

© 2005 BioMed Central Ltd

Poster presentation

Imbalance in cytokine homeostasis is thought to play an important part in the pathogenesis of chronic inflammatory diseases such as rheumatoid arthritis. We demonstrated that T cells might exert a pathological effect through direct cellular contact with monocyte-macrophages, inducing a massive upregulation of IL-1β and tumour necrosis factor (TNF) [1]. We showed that this mechanism that might be relevant to chronic inflammation is specifically inhibited by high-density lipoproteins (HDL) [2]. Like many other stimuli, besides proinflammatory cytokines, the contact-mediated activation of monocytes induces the production of cytokine inhibitors such as IL-1Ra. HDL inhibited the production of IL-1β and TNF but not that of IL-1Ra induced in monocytes activated by membranes isolated from stimulated T cells to mimic cellular contact. This was also the case in peripheral blood mononuclear cells stimulated by either phytoheamagglutinin or tetanus toxoid. Similarly, IL-1Ra mRNA expression was not inhibited contrary to IL-1β and TNF mRNA. This demonstrates that different molecules at the surface of stimulated HUT-78 cells are involved in the induction of IL-1β, TNF and IL-1Ra in monocytes, IL-1β and TNF being activated by HDL-specific ligand(s). Separation of CHAPS-solubilized membrane molecules by liquid isoelectric focusing showed that two activity peaks were present; one activating IL-1β, TNF and IL-1Ra production, the other inducing the production of IL-1Ra in the absence of IL-1β and TNF. Further isolation of these two types of factor by gel filtration demonstrated that factor(s) inducing IL-1β, TNF and IL-1Ra displayed a Mr around 40,000 kDa, whereas factors inducing IL-1Ra only displayed Mr around 70,000 kDa and 30,000 kDa. Thus different factors are expressed at the surface of stimulated T cells that differentially trigger the production of proinflammatory and anti-inflammatory factors, and are differently affected by HDL.

References

  1. Burger D, Roux-Lombard P, Chizzolini C, Dayer JM: Cell–cell contact in chronic inflammation: the importance to cytokine regulation in tissue destruction and repair. In Cytokines and Joint Injury. Edited by van den Berg WB, Miossec P Basel. Birkhäuser Verlag; 2004:165-188.

    [Parnham MJ (Series Editor): Progress in Inflammation Research.]

    OpenURL

  2. Hyka N, Dayer JM, Modoux C, Kohno T, Edwards CK III, Roux-Lombard P, Burger D: Apolipoprotein A-I inhibits the production of interleukin-1beta and tumor necrosis factor-alpha by blocking contact-mediated activation of monocytes by T lymphocytes.

    Blood 2001, 97:2381-2389. PubMed Abstract | Publisher Full Text OpenURL