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Mol Immunol. 2008 Nov;46(1):91-6. doi: 10.1016/j.molimm.2008.07.006. Epub 2008 Aug 27.

Functional antagonism by GM-CSF on TNF-alpha-induced CD83 expression in human neutrophils.

Author information

1
Department of Respiratory Medicine, University Medical Center Utrecht (UMCU), Heidelberglaan 100, 3584CX Utrecht, Netherlands.

Abstract

TNFalpha-induced expression of CD83 in leukocytes is mediated by NF-kappab. The aim of our present study was to investigate the underlying mechanism of a unique functional antagonism between GM-CSF and TNFalpha-induced up-regulation of CD83 in human neutrophils. CD83 was down-regulated by co-stimulation of neutrophils with TNFalpha and GM-CSF compared to TNFalpha alone both at the level of mRNA and protein. In marked contrast, the expression of IL-1RA was up-regulated under the same conditions. The down-regulation of CD83 was not mediated by modulation of the NF-kappab signaling pathway. Neither was it mediated by a decrease in mRNA stability of CD83. NF-kappab was modulated under these conditions as both the expression of the target gene IL-1RA as well as the phosphorylation of IkBalpha were up-regulated. Our results show that co-stimulation with pro-inflammatory cytokines such as TNFalpha and GM-CSF can have differential effects on inflammatory pathways initiated in the same target cell. GM-CSF can both synergize with TNFalpha in the case of expression of IL1-RA and antagonize in the case of CD83. Therefore, expression of CD83 as read out for activation of neutrophils in patients with inflammatory diseases is complicated by the presence of cross-modulating cytokines such as GM-CSF.

PMID:
18755511
DOI:
10.1016/j.molimm.2008.07.006
[Indexed for MEDLINE]

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