INVOLVEMENT OF CYTOKINES, DNA-DAMAGE, AND REACTIVE OXYGEN INTERMEDIATES RADIATION-INDUCED MODULATION OF INTERCELLULAR-ADHESION MOLECULE-1 EXPRESSION

By virtue of its capacity to serve as a counter-receptor for lymphocyt e function-associated antigen-1, intercellular adhesion molecule-1 (IC AM-1) plays a pivotal role in generation and maintenance of immunologi c/inflammatory skin diseases by mediating leukocyte/keratinocyte adhes ion, Ultraviolet radiation (UVR) may exert both antiinflammatory effec ts (e.g., UV phototherapy) and proinflammatory effects (e.g., triggeri ng of photosensitive skin diseases) on human skin, Recent evidence ind icates that UVR-induced changes of keratinocyte ICAM-1 expression cons titute the molecular basis for these ambivalent properties of UVR, as UVR is able to exert two separate and even opposite effects on ICAM-1 expression, As an antiinflammatory effect, UVR may inhibit cytokine-in duced up-regulation of keratinocyte ICAM-1 expression, whereas inducti on of ICAM-1 expression by UVR represents a proinflammatory activity, This latter effect is mediated by an autocrine mechanism involving int erleukin (IL)-1 alpha. In this autocrine system, UVR exposure of human keratinocytes leads to the release of IL-1 alpha, which in turn up-re gulates the expression of IL-1 receptor type 1 molecules on the kerati nocyte surface, thereby increasing the sensitivity of these cells towa rd IL-1 alpha. As a consequence, irradiated keratinocytes are capable of responding to endogenously produced IL-la by increasing ICAM-1 expr ession, Modulation of keratinocyte ICAM-1 expression after UVR exposur e may be observed after both short-wave UVR (UVB; 280-320 nm) and long wave UVR (UVA1; 340-400 nm), The photobiologic mechanisms underlying U VB versus UVA1 radiation-induced ICAM-1 modulation have been found to differ. Although not completely delineated, UVB radiation-induced modu lation of ICAM-1 expression appears to be mediated via the induction o f DNA damage, whereas UVA1 radiation effects involve the generation of reactive oxygen intermediates.