Avtor/Urednik		Švajger, Urban; Vidmar, Alenka; Jeras, Matjaž
Naslov		Niflumic acid renders dendritic cells tolerogenic and up-regulates inhibitory molecules ILT3 and ILT4
Tip		članek
Vir		Int Immunophar
Vol. in št.		Letnik 8, št. 7
Leto izdaje		2008
Obseg		str. 997-1005
Jezik		eng
Abstrakt		Niflumic acid is a member of non-steroidal anti-inflammatory agents, from which aspirin was recently shown to inhibit maturation of human-monocyte derived dendritic cells (DCs). DCs are crucial regulators of the immune response, capable of inducing immunity as well as tolerance. In our in vitro study we showed a tolerogenic effect of NFA on phenotype and function of LPS-matured monocyte-derived DCs. Different drug concentrations dose-dependently down-regulated the expression of co-stimulatory molecules, particularly CD80 and lowered the expression of dendritic cell marker CD1a. Opposingly, the expressions of two inhibitory surface molecules, associated with tolerogenic DCs, immunoglobulin-like transcripts (ILT)3 and ILT4 were induced in treated DCs. The levels of TNFalpha production by NFA-treated DCs did not change significantly compared to controls, whereas the IL-12p70 and IL-10 production was completely abrogated at higher drug concentrations. However, at lower drug concentrations, the production of IL-12p70 was increased. There were no significant differences in the uptake of FITC labeled dextran by treated DCs compared to untreated cells. In allogeneic cultures with whole CD4+ T cells, dendritic cells differentiated in the presence of NFA appeared poor stimulators of CD4+ T-cell proliferation, even compared to immature DCs (iDCs). These results indicate the immunosuppressive properties of NFA, which may be therapeutically useful in controlling chronic immune and/or inflammatory diseases, by modulating DC characteristics towards tolerogenic DCs.
Deskriptorji		DENDRITIC CELLS NIFLUMIC ACID FLOW CYTOMETRY T-LYMPHOCYTES CYTOKINES CELLS, CULTURED CD4-POSITIVE T-LYMPHOCYTES ANTIGENS, CD14 ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL CELL DIFFERENTIATION CHLORIDE CHANNELS CYCLOOXYGENASE INHIBITORS ENDOCYTOSIS IMMUNOSUPPRESSIVE AGENTS INTERLEUKIN-10 INTERLEUKIN-12 MEMBRANE GLYCOPROTEINS RECEPTORS, CELL SURFACE RECEPTORS, IMMUNOLOGIC