Interaction between galectin-3 and Fc gamma RII induces down-regulation ofIL-5 gene: implication of the promoter sequence IL-5REIII

Our previous work demonstrated the capacity of galectin-3 (a P-galactoside binding animal lectin) to inhibit IL-5 gene expression in different cell ty pes, but the interaction of lectin with the cells and the pathways for tbe inhibition process are unknown. One of the purposes of this work was to stu dy the cellular ligand for galectin-3. We have demonstrated that galectin-3 can bind to the low affinity IgG receptor (Fc gamma RII or CD32) by using different experimental approaches, such as flow cytometry, fusion protein G ST technology, and with a model of Fc gamma RII-deficient mice. To further analyze the interaction between Fc gamma RII and galectin3, and its implica tion in IL-5 gene down-regulation we used Fc gamma RII-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 Fc gam ma RIII-deficient mice were incubated with galectin3, IL-5 gene expression was down-regulated, Finally, we studied the implication of the negative reg ulatory sequence in the IL-5 gene promoter. In the presence of galectin3, a DNA-protein complex was formed with the IL-5REIII region. This complex was not observed when unrelated oligonucleotide was used, So, galectin3 induce s a pathway, which activates a transcription factor that binds to IL-5REIII , This interaction is capable of inhibiting IL-5 gene transcription.