Inhibition of Skin Allograft Rejection and Acute Graft-Versus-Host Disease by Cis-Urocanic Acid

Urocanic Acid Photochemistry and Photobiology

“…It has been demonstrated that such PUVA treatment is associated with immunosuppression, and this phenomenon has been attributed to 8-MOP-photosensitized isomerization of tUA in the skin (37). More recent in virro studies support this proposal (76).…”

“…Other examples include (i) a Hypersil APS glass column (100 X 3 mm i.d., 5 pm particle size) that provides a detection limit for both isomers at a signal-to-noise ratio of 3 of a 3 nM solution for the 60 fmol injected sample (34); (ii) a 200 X 3 mm i.d. column packed with Chromsphere C18 (5 pm particle size) eluted with 5% acetonitrile in 20 mM potassium dihydrogen phosphate (pH 3.7) containing 1 g/L of sodium heptanesulfonate (35); (iii) a Novapak C18 column (150 X 3.9 mm i.d., 4 pm particle size) with 10 mM acetic acid (pH 5) (36); (iv) a Tosoh ODS 8OTS column (250 X 4.6 mm i.d., 7 pm particle size) with a mobile phase consisting of 7% acetonitrile in 20 mM potassium dihydrogenphosphate containing 1 g/L sodium heptanesulfonate, pH 3.7 (adjusted with 14.7 mM phosphoric acid) (18) (the response of the two isomers is linear under these HPLC conditions in the range of 1.5 nmol to 2 pmol (0.276 ng) per injection and the detection limit for each isomer was 2 pmol at a signal-to-noise ratio of 5:l); (v) an ODS Hypersil column (100 mm X 2 mm i.d., 3 pm particle size) with the mobile phase consisting of 10 mM ammonium phosphate (pH 5) and 2 mM tetrabutylammonium bromide (37,38); (vi) a LiChrosorb NH, Hibar 250-4 column (250 X 4 mm i.d., 5 pm particle size) with 50% acetonitrile in 50 n M potassium phosphate (pH 5) with a detection limit of 0.1 g/mL (27); (vii) a LiChrosorb RP 18 column (250 X 4 mm i.d., 5 pm particle size) with 2% acetonitrile in 100 mM sodium perchlorate (pH 3) with reported capacity factors of 3.25 and 2.60 for cUA and tUA, respectively, a resolution of 1.25 and a detection limit of 0.1 ng of both isomers (39); (viii) a C l 8 analytical column using a gradient of acetonitrile in 20 mM acetate buffer (pH 6.5) with reported detection limits for the UA isomers of 0.1 pmoVmL and a quantification limit for UA isomers extracted from the skin of 0.3 pg (40) and (ix) a 250 X 4 mm i.d. reversed-phase p-Bondapak column with 50 mM phosphate buffer (pH 3.4-3.6) containing 1-3 mM sodium octane sulfonate and 2 4 % methanol (41).…”

“…presumably due to leakage of UVB radiation from the UVA light sourcc (37). Whether these in vitro studies of 8-MOP are responsible for the in vivo immunosuppression remains to be determined.…”

cis-Urocanic Acid Initiates Gene Transcription in Primary Human Keratinocytes

“…This observation was the basis for proposing trans-UCA as a photoreceptor for UVR-induced immune suppression (8). Subsequent studies in mice have demonstrated that topical or systemic application of cis-UCA mimics many aspects of UVR-induced immune suppression, including suppression of CHS and delayed-type hypersensitivity responses (9 -12), tumor Ag presentation (13,14), depletion of Langerhans cells (15), and inhibition of allograft rejection and graft-vs-host disease (16,17). Neutralization studies using a mAb against cis-UCA also restored many of the effects of UVR on the immune responses (18,19).…”

Cytokines and Photocarcinogenesis

“…Urocanic acid exists primarily as the trans-isomer in the epidermis but exposure to UVB radiation induces an isomerization to the cis-isomer (42,43). Cis-but not trans-UCA inhibits DTH to herpes simplex virus in mice, inhibits allograft rejection (44) and acute graft versus host disease in mice (45) and, when given systematically, initiates an antigen presentation defect in splenic dendritic cells (46). It does not, however, inhibit mitogen-induced lymphocyte transformation (47).…”