Naslov
Effects of immunomodulatory drugs on galectin-3

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

Izvornik
Glycobiology (0959-6658) 14 (2004), 11;

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, kongresno priopcenje, znanstveni

Ključne riječi
galectin-3; immunomodulatory drugs

Sažetak
Galectin-3, a 29-32 kDa  -galactoside binding lectin, is implicated in many biological processes, (e.g. growth regulation, pre-mRNA splicing, cell differentiation, neoplastic transformation and tumor metastasis). It plays a key role in immune responses by modulating T-cell apoptosis, proliferation, cell adhesion, chemotaxis and synthesis of inflammatory mediators such as cytokines, nitric oxide and prostaglandines. Galectin-3 expression is influenced by various stimuli but the precise regulatory mechanisms are not yet elucidated. In our previous studies we showed the involvement of the NF-kappaB and AP-1 transcription factors in regulation of galectin-3 expression. It was also shown that galectin-3 expression in macrophages is regulated by Ras/MAP kinase signalling pathway. The mentioned transcription factors and signalling pathway are strongly influenced by many anti-inflammatory drugs. Therefore, the aim of our study was to determine the effects of steroid (hydrocortisone - HC and dexamethasone - Dex) as well as non-steroid immunomodulatory drugs (aspirin – Asp and indomethacin - Ind) on the expression of galectin-3 both on the mRNA and protein level. The human monocytic cell line THP-1 was exposed to various concentrations of Asp (0.1, 0.5, 1 and 2 mM), Ind (0.1, 1, 5 and 10 μ M), HC (0.1, 1, 5 and 10 μ M) and Dex (0.1, 1, 10 and 100 nM) during 1, 3, 5, 24, 48 or 72 hrs. The target gene mRNA level is evaluated using relative RT-PCR method and GeneScan analysis software. The results showed that all concentrations of applied drugs halved the galectin-3 mRNA level already after 1 h of exposure (except 0.1 mM aspirin which showed that effect after 24 h) and that the level of mRNA continued to decrease during time and was only 4-30% of the initial value after 72 h. Surprisingly, the protein expression measured by chemiluminescent-western blot analysis didn’ t follow the same pattern – the decrease was observed only after 48 and 72 h of exposure, when the galectin-3 level fall on 70% and 50% of the initial value, respectively.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA