Inhibition of intercellular adhesion molecule‐1 (ICAM‐1) expression in ultraviolet B‐irradiated human antigen‐presenting cells is restored after repair of cyclobutane pyrimidine dimers

Abstract

The present study assessed the molecular mechanism underlying ultraviolet (UV) B radiation-induced inhibition of the expression of the adhesion molecule ICAM-1 in human antigen-presenting cells (APC). UVB radiation-induced inhibition of ICAM-I expression in human peripheral blood monocytes was associated with the generation of cyclobutane pyrimidine dimers (CPD). CPD were reduced by 60% after treatment with liposomal packed photolyase, an enzyme which removes CPD after absorption of photoreactivating light. Although incomplete, reduction of CPD was associated with complete restoration of ICAM-1 expression at the mRNA and protein level. Neither reduction of CPD level nor restoration of ICAM-1 expression were observed, if monocytes were treated with empty liposomes, or if they were irradiated with photoreactivating light prior to application of photolyase. DNA damage might also induce soluble mediators capable of autocrine inhibition of ICAM-1 expression. UVB irradiation of monocytes did not induce IL-10 production, but resulted in release of prostaglandin (PG) E2. Treatment of unirradiated monocytes with PGE2 completely inhibited ICAM-1 expression, thus mimicking the UVB effect. Inhibition of monocytic PGE2 production by indomethacin, however, did not restore ICAM-1 expression. These results suggest that formation of CPD is necessary and sufficient for UVB radiation-induced inhibition of ICAM-1 expression. In contrast, PGE2 might serve a paracrine role in UVB radiation-induced immunosuppression.

Dietary compound ellagic acid alleviates skin wrinkle and inflammation induced by UV‐B irradiation

“…Alterations in cutaneous and systemic immunity occur as a result of the UV‐induced inflammation (30,31). These changes lead to the generation of suppressor T cells, the induction of antigen‐specific immunosuppression and the lowering of cell‐mediated immunity.…”

“…Cell adhesion molecules play a key role in the induction of the immune response and in the pathogenesis of inflammation. UV exposure induces inflammation and damage, including alteration of adhesion molecule expression and loss of antigen‐presenting cell function within the skin (31). This study revealed that ellagic acid diminished the increased ICAM‐1 expression of HaCaT keratinocytes caused by UV‐B radiation.…”

Ultraviolet B Radiation-Mediated Inhibition of Interferon-γ-Induced Keratinocyte Activation Is Independent of Interleukin-10 and Other Soluble Mediators But Associated with Enhanced Intracellular Suppressors of Cytokine-Signaling Expression

“…The involvement of both DNA damage (Krutmann and Grewe, 1995) and IFN-g unresponsiveness due to inhibition of signal transduction molecules has been suggested. Grawe and coworkers demonstrated that in human antigen-presenting cells the inhibition of ICAM-1 expression by UVBR is achieved via the generation of cyclobutane pyrimidine dimers (Grewe et al, 2000). Aragane and coworkers demonstrated that UVR inhibits the phosphorylation of the signal transduction and transcription factor (STAT)-1, which is essential for mediating signals of several cytokines, including IFN-g.…”

UV-specific DNA repair recombinant fusion enzyme: A new stable pharmacologically active principle suitable for photoprotection

“…Repairing and reducing the dimers in the UVdamaged DNA prevents the immunosuppression [21] and consequently also prevents mutations from being fixed.…”