Physiologic doses of urocanic acid do not alter the allostimulatory function or the development of murine dendritic cells in vitro

Abstract

Exposure to UVB results in the isomerization of trans-urocanic acid (UCA), localized in the stratum corneum, to cis-UCA. Cis-UCA can mediate at least some of the immunosuppressive effects of UVB, though the mechanism of cis-UCA action remains incompletely defined. Alterations in Langerhans cells, and other dendritic antigen presenting cell populations in the skin, may contribute to the loss of skin immune function following UVB exposure. Hence, this study was designed to investigate whether cis-UCA directly can induce changes in the immunostimulatory capacity of dendritic cells (DC) and the development of DC from precursor cells. Murine DC were generated from C57BL/6 bone marrow (BM) using granulocyte-macrophage colony-stimulating factor (GM-CSF), and were used as stimulator cells in mixed lymphocyte reactions (MLR) using BALB/c lymph node cells (LNC) as responders. The addition of cis- and trans-UCA at concentrations ranging from 0.1-500 micrograms/ml to the MLR did not affect proliferative responses. Cis- or trans-UCA (100 micrograms/ml) was added to GM-CSF stimulated mouse BM cells on day 0, day 3 or day 5 of culture, and the phenotype and allo-stimulatory function of the DC were analysed on day 7. Treatment with cis- or trans-UCA did not affect the numbers or the viability of cells in the BM cultures. In addition, the expression on DC of Iab, 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 results suggest that cis-UCA does not exert its immunosuppressive activity through direct effects on DC. Such activity may be independent of DC, or alternatively, cis-UCA may influence DC function indirectly, through the induction of secondary mediators.

IL-12 Prevents the Inhibitory Effects of cis-Urocanic Acid on Tumor Antigen Presentation by Langerhans Cells: Implications for Photocarcinogenesis

“…These reports are in agreement with the finding that cis-UCA altered vimentin expression among LC, leading to the destruction of their cytoskeleton and reduced APC function (46). Additionally, cis-UCA was able to significantly suppress the mixed epidermal cell lymphocyte reaction, but murine bone marrow-derived dendritic cells exposed to cis-UCA demonstrated only feeble impairment of their allostimulatory capacity (47,48). Although the epidermal cell suspensions we used were enriched for LC, we were not using purified LC.…”

In vitro and in vivo activation of hypericin with the incoherent light source PDT 1200 SOA (520–750 nm) and with solar simulated radiation (290–2500 nm)

“…A dark control was included in each experiment. After irradiation, the cells were washed and further cultured with medium for 48 h. Cell proliferation was determined by [ 3 H] -TdR incorporation as described by Lappin et al (17). Data are expressed as mean c.p.m.∫SD of triplicate wells.…”

cis-Urocanic Acid does not Induce the Expression of Immunosuppressive Cytokines in Murine Keratinocytes¶†

“…For example, incubation of epidermal cells with cis-UCA suppressed the mixed skin cell-lymphocyte reaction (32), downregulated antitumor immune responses (25) and inhibited the induction phase of contact hypersensitivity (33). On the other hand, cis-UCA did not induce the release of soluble mediators from mouse keratinocytes (34) and had no direct effect on the antigen presenting ability of dendritic cells (35) or Langerhans cells (36).…”