engleski

GALECTIN-3 EXPRESSION IS AFFECTED BY GLUCOCORTICOIDS

Galectin-3, a beta-galactoside binding lectin, acts as a strong pro-inflammatory signal that modulates cell proliferation and adhesion, chemotaxis, phagocytosis and synthesis of inflammatory mediators. However, data on regulatory mechanisms of galectin-3 expression are still elusive. We have previously shown that transcription factors NF- B and AP-1 are involved in regulation of galectin-3 expression. Since signaling pathways that regulate the activity of these transcription factors are strongly influenced by glucocorticoids we investigated effects of hydro¬ cortisone and dexamethasone, applied in therapeutic ranges, on the expression of LGALS3 and galectin-3 in non-differentiated and differentiated cells of monocytic THP-1 cell-line during 72 hours of cultivation. Relative RT-PCR method and GeneScan analysis software were used for assessing galectin-3 mRNA level and chemiluminescent-western blot analysis was used for measuring galectin-3 level. Differentiation of monocytic THP-1 cells into macrophages strongly induced expression of LGALS3 and galectin-3. In undifferentiated cells both drugs (in all applied concentrations) inhibited expression of LGALS3 and galectin-3, and inhibitory effect correlated with time of exposure. In differentiated cells, hydrocortisone and dexamethasone inhibited LGALS3 expression at the beginning, but during further incubation constitutive level of galectin-3 mRNA was reestablished. On the protein level, prolonged exposure to both drugs induced galectin-3 expression. The chosen glucocorticoid drugs affected LGALS3 and galectin-3 expression, and their effects depended on cell differentiation level, concentration of the applied drug as well as time of exposure. These findings represent important step in the understanding of the effects of glucocorticoids on galectin-3 in monocytes/macrophages, hence on their immunomodulatory activities.

galectin-3; immunomodulatory drugs

nije evidentirano