Naslov
Galectin-3-a novel target molecule of immunomodulatory drugs

Autori
Dabelić, Sanja ; Flogel, Mirna ; Dumić, Jerka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Glycoproteomics: protein modifications for versatile functions / Dumić, Jerka ; Flogel, Mirna - Zagreb : Farmaceutsko-biokemijski fakultet Sveučilišta u Zagrebu, 2005

Skup
Glycoproteomics: protein modifications for versatile functions

Mjesto i datum
Dubrovnik, Hrvatska, 28.06.2005. - 30.06.2005

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
galectin-3; immunomodulatory drugs

Sažetak
Galectin-3, a β -galactoside binding lectin, acts as a strong pro-inflammatory signal that modulates cell proliferation and adhesion, chemotaxis, phagocytosis and synthesis of inflammatory mediators. Its expression is influenced by various endogenous and exogenous stimuli but the precise regulatory mechanisms are not yet elucidated. We have previously shown the involvement of the transcription factors NF- B and AP-1 in regulation of galectin-3 expression through the binding sites present in the promoter region of galectin-3 gene (LGALS3). Many immunomodulatory drugs affect signaling pathways that regulate the activity of these transcriptional factors. Therefore, the aim of our study was to determine the effects of steroidal (hydrocortisone - HC and dexamethasone - Dex) and non-steroidal immunomodulatory drugs (aspirin – Asp and indomethacin - Ind), 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. None of the studied drugs in applied concentrations during 72 hours of cultivation had cytotoxic effect on the cells. The targeted mRNA level was evaluated using relative RT-PCR technique and analysis on the AbiPrism 310 Genetic Analyser. Galectin-3 expression in cell homogenates was determined by western-immunoblot analysis. The results showed that chosen immunomodulatory drugs affected LGALS3 and galectin-3 expression and that their effects depended on cell differentiation level, concentration of the applied drug, and time of exposure. In undifferentiated cells all studied drugs in all applied concentrations inhibited expression of LGALS3 and galectin-3, and inhibitory effect correlated with time of exposure. Differentiation of monocytic THP-1 cells into macrophages during 48-hours strongly induced expression of LGALS3 (3 times) and galectin-3 (3.5 times). In differentiated cells, all studied drugs 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 all applied drugs induced galectin-3 expression. Intensity and time-course of both, mRNA and protein level changes depended on drug type and on applied concentration. These findings suggest that the applied immunomodulatory drugs affect different signaling pathways and mechanisms of regulation of galectin-3 expression, on both mRNA and protein level.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA