PHYSIOLOGICAL DOSES OF UROCANIC ACID DO NOT ALTER THE ALLOSTIMULATORYFUNCTION OR THE DEVELOPMENT OF MURINE DENDRITIC CELLS IN-VITRO

Exposure to UVB results in the isomerization of trans-urocanic acid (U CA), localized in the stratum corneum, to cis-UCA. Cis-UCA can mediate at least some of the immunosuppressive effects of UVB, though the mec hanism of cis-UCA action remains incompletely defined. Alterations in Langerhans cells, and other dendritic antigen presenting cell populati ons in the skin, may contribute to the loss of skin immune function fo llowing UVB exposure. Hence, this study was designed to investigate wh ether cis-UCA directly can induce changes in the immunostimulatory cap acity of dendritic cells (DC) and the development of DC from precursor cells. Murine DC were generated from C57BL/6 bone marrow (BM) using g ranulocyte-macrophage colony-stimulating factor (GM-CSF), and were use d as stimulator cells in mixed lymphocyte reactions (MLR) using BALB/c lymph node cells (LNC) as responders. The addition of cis-and trans-U CA at concentrations ranging from 0.1-500 mu g/ml to the MLR did not a ffect proliferative responses. Cis- or trans-UCA (100 mu g/ml) was add ed to GM-CSF stimulated mouse BM cells on day 0, day 3 or day 5 of cul ture, and the phenotype and allo-stimulatory function of the DC were a nalysed on day 7. Treatment with cis-or trans-UCA did not affect the n umbers or the viability of cells in the BM cultures. In addition, the expression on DC of Ia(b), CD11c or the costimulatory molecules ICAM-1 , B7-1, B7-2 and CD40 was not altered by the addition of cis-UCA to BM cultures. The inability of cis-UCA to alter the development of DC in vitro was confirmed by analysing the functional capacity of DC in MLR. DC generated in the presence of cis-UCA were equally efficient in the induction of allo-stimulation, when compared with control DC. These r esults suggest that cis-UCA does not exert its immunosuppressive activ ity through direct effects on DC. Such activity may be independent of DC, or alternatively, cis-UCA may influence DC function indirectly, th rough the induction of secondary mediators.