International Immunology, Vol. 12, No. 4, 547-554,
April 2000
© 2000 Japanese Society for Immunology
Stimulation of Fc
R receptors induces monocyte chemoattractant protein-1 in the human monocytic cell line THP-1 by a mechanism involving I
B-
degradation and formation of p50/p65 NF-
B/Rel complexes
Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Facultad de Medicina, 47005 Valladolid, Spain
Correspondence to: M. Sánchez Crespo
THP-1 monocytic/macrophage cells were stimulated via their Fc
R receptors with insoluble aggregates of human IgG and the production of the CC chemokine monocyte chemoattractant protein (MCP)-1 assayed. A dose- and time-dependent production of MCP-1 comparable to that produced by the most potent agonists could be detected in the culture medium by a sensitive ELISA assay. This was accompanied by a parallel activation of the transcription factor NF-
B as judged from both the appearance of
B-binding activity containing p50/p65 NF-
B/Rel complexes in the nuclear extract and the disappearance of the NF-
B inhibitor I
B-
in the cell lysate. In contrast, I
B-ß and I
B-
expression was not modified, thus pointing to the occurrence of a selective degradation of I
B-
under those conditions. Attempts to modulate MCP-1 production with compounds that display inhibitory effects on the activation of NF-
B such as the proteasome inhibitor N-acetyl-leucinyl-leucinyl-norleucinal, the antioxidant pyrrolidine dithiocarbamate and the salicylate derivative 2-hydroxy-4-trifluoromethylbenzoic acid showed a parallel effect on both MCP-1 production and NF-
B activation, thus pointing to the involvement of
B-binding sites on the transcriptional regulation of MCP-1 production. Our findings suggest the existence in monocytic cells of a signaling mechanism initiated by cross-linking of low-affinity Fc
R, most likely of the Fc
RII family since THP-1 cells do not express Fc
RIII receptors, that involves activation of NF-
B associated to the proteolytic degradation of I
B-
and leads to the transcriptional up-regulation of MCP-1.
Keywords: chemokines, Fc receptors, inflammation, monocytes/macrophages, transcription factors
Transmitting editor: E. R. Unanue
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