Stimulation of Fc gamma R receptors induces monocyte chemoattractant protein-1 in the human monocytic cell line THP-1 by a mechanism involving I kappa B-alpha degradation and formation of p50/p65 NF-kappa B/Rel complexes
A. Alonso et al., Stimulation of Fc gamma R receptors induces monocyte chemoattractant protein-1 in the human monocytic cell line THP-1 by a mechanism involving I kappa B-alpha degradation and formation of p50/p65 NF-kappa B/Rel complexes, INT IMMUNOL, 12(4), 2000, pp. 547-554
THP-1 monocytic/macrophage cells were stimulated via their Fc gamma R recep
tors with insoluble aggregates of human IgG and the production of the C-C c
hemokine monocyte chemoattractant protein (MCP)-1 assayed. A dose- and time
-dependent production of MCP-1 comparable to that produced by the most pote
nt agonists could be detected in the culture medium by a sensitive ELISA as
say. This was accompanied by a parallel activation of the transcription fac
tor NF-kappa B as judged from both the appearance of Ice-binding activity c
ontaining p50/p65 NF-kappa B/Rel complexes in the nuclear extract and the d
isappearance of the NF-kappa B inhibitor I kappa B-alpha in the cell lysate
, In contrast, I kappa B-beta and I kappa B-epsilon expression was not modi
fied, thus pointing to the occurrence of a selective degradation of I kappa
B-alpha under those conditions. Attempts to modulate MCP-1 production with
compounds that display inhibitory effects on the activation of NF-kappa B
such as the proteasome inhibitor N-acetyl-leucinyl-leucinyl-norleucinal, th
e antioxidant pyrrolidine dithiocarbamate and the salicylate derivative 2-h
ydroxy-4-trifluoromethylbenzoic acid showed a parallel effect on both MCP-1
production and NF-kappa B activation, thus pointing to the involvement of
kappa B-binding sites on the transcriptional regulation of MCP-1 production
. Our findings suggest the existence in monocytic cells of a signaling mech
anism initiated by cross-linking of low-affinity Fc gamma R, most likely of
the Fc gamma RII family since THP-1 cells do not express Fc gamma RIII rec
eptors, that involves activation of NF-kappa B associated to the proteolyti
c degradation of I kappa B-alpha and leads to the transcriptional upregulat
ion of MCP-1.