Epidermal Urocanic Acid and Suppression of Contact Hypersensitivity by Ultraviolet Radiation in <i>Monodelphis domestica</i>

Abstract

A single specific epidermal photoreceptor for the immunosuppressive action of UV radiation has not been defined, although separate evidence is accruing in favour of each of two candidates, trans-mocamc acid and DNA. In Monodelphis domestica, specific photoreactivation repair of UV radiation-induced pyrimidine dimers has been shown to abrogate the suppression of contact hypersensitivity (CHS), thus suggesting that DNA is the target for this impairment. However, in both haired and hairless mice, immunosuppressive effects of UV radiation have been reproduced by the exogenous administration of the UV photoproduct of urocanic acid, cis-urocanic acid. We show here that the epidermis of M. domestica contains urocanic acid, that UV irradiation of the shaved dorsal skin has resulted in an increase in epidermal cis-urocanic acid and that the topical application of a cis-urocanic acid-containing lotion significantly depressed the capacity of Monodelphis to respond to contact sensitisers, in a manner analogous to these responses in the hairless mouse. Therefore in Monodelphis, suppression of CHS by UV irradiation appears to involve both urocanic acid photo-isomerisation and epidermal DNA damage.

<i>Ci</i><i>s</i>-Urocanic-Acid-lnduced Suppression of Contact Hypersensitivity in <i>Monodelphis domestica</i> Is Prevented by Ultraviolet A Radiation/Photoreactivating Light

“…It would be interesting to test the effect of PRL exposure prior to a less severely immunosuppressive UVB dose (approximate ly 90% suppression of contact hypersensitivity was induced by UVB [3], whereas m-urocanic acid induced approxi mately 50% suppression). Alternatively, it is possible that m -urocanic acid is in fact not involved in the UVB-induced immunosuppression in M. domestica [7].…”

“…How ever, in both mouse and, more recently, in M. domestica, substantial evidence has also accrued to implicate epider mal fra«.v-urocanic acid as the critical photoreceptor for UVB-induced immunosuppression and its photoproduct, cA-urocanic acid, as the immunosuppressive molecule. Treatment with exogenous cA-urocanic acid effectively suppresses immune function in both the mouse and opos sum [4][5][6][7]. Thus far, no immunologically relevant interac tive role of cA-urocanic acid with DNA has been revealed.…”

Ultraviolet light induced injury: Immunological and inflammatory effects

“…From the accumulating evidence it is clear that UCA has a major role in UV‐induced immunosuppression of DTH responses and a lesser one in CHS responses. However, the actions of cis ‐UCA do not exclude DNA damage being important as both UCA and DNA mediate effects associated with immunosuppression 189 …”

“…However, the actions of cis-UCA do not exclude DNA damage being important as both UCA and DNA mediate effects associated with immunosuppression. 189…”

Interaction of UVB-absorbing Sunscreen Ingredients with Cutaneous Molecules May Alter Photoimmune Protection¶

“…Several photoreceptors for the immune impairment have been identified; a primary contender for this role is epidermal trans-urocanic acid (5,6), which is photoisomerized to cis-urocanic acid in irradiated skin. The cis isomer has immunosuppressive properties similar to those of UVB radiation, which can be observed with exogenous cis-urocanic acid applied topically (7)(8)(9) or parenterally (10) to mice. On the other hand, DNA damage (11,12), histamine (13), inflammatory prostaglandins (14) and reactive oxygen species (15) also appear to be relevant mediators of immunosuppression.…”