Interaction between galectin-3 and FcgammaRII induces down-regulation of IL-5 gene: implication of the promoter sequence IL-5REIII.

Abstract

Our previous work demonstrated the capacity of galectin-3 (a beta-galactoside binding animal lectin) to inhibit IL-5 gene expression in different cell types, but the interaction of lectin with the cells and the pathways for the inhibition process are unknown. One of the purposes of this work was to study the cellular ligand for galectin-3. We have demonstrated that galectin-3 can bind to the low affinity IgG receptor (FcgammaRII or CD32) by using different experimental approaches, such as flow cytometry, fusion protein GST technology, and with a model of FcgammaRII-deficient mice. To further analyze the interaction between FcgammaRII and galectin-3, and its implication in IL-5 gene down-regulation we used FcgammaRII-deficient mice. When PBMC from these mice were incubated with galectin-3, the expression of the IL-5 gene was unchanged. However, when PBMC from wild type mice and FcgammaRIII-deficient mice were incubated with galectin-3, IL-5 gene expression was down-regulated. Finally, we studied the implication of the negative regulatory sequence in the IL-5 gene promoter. In the presence of galectin-3, a DNA-protein complex was formed with the IL-5REIII region. This complex was not observed when unrelated oligonucleotide was used. So, galectin-3 induces a pathway, which activates a transcription factor that binds to IL-5REIII. This interaction is capable of inhibiting IL-5 gene transcription.