title: Involvement of cytokines, DNA damage, and reactive oxygen intermediates in ultraviolet radiation-induced modulation of intercellular adhesion molecule-1 expression.
abstract: By virtue of its capacity to serve as a counter-receptor for lymphocyte function-associated antigen-1, intercellular adhesion molecule-1 (ICAM-1) plays a pivotal role in generation and maintenance of immunologic/inflammatory skin diseases by mediating leukocyte/keratinocyte adhesion. Ultraviolet radiation (UVR) may exert both antiinflammatory effects (e.g., UV phototherapy) and proinflammatory effects (e.g., triggering of photosensitive skin diseases) on human skin. Recent evidence indicates that UVR-induced changes of keratinocyte ICAM-1 expression constitute 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-induced up-regulation of keratinocyte ICAM-1 expression, whereas induction of ICAM-1 expression by UVR represents a proinflammatory activity. This latter effect is mediated by an autocrine mechanism involving interleukin (IL)-1 alpha. In this autocrine system, UVR exposure of human keratinocytes leads to the release of IL-1 alpha, which in turn up-regulates the expression of IL-1 receptor type 1 molecules on the keratinocyte surface, thereby increasing the sensitivity of these cells toward IL-1 alpha. As a consequence, irradiated keratinocytes are capable of responding to endogenously produced IL-1 alpha by increasing ICAM-1 expression. Modulation of keratinocyte ICAM-1 expression after UVR exposure may be observed after both short-wave UVR (UVB; 280-320 nm) and long-wave UVR (UVA1; 340-400 nm). The photobiologic mechanisms underlying UVB versus UVA1 radiation-induced ICAM-1 modulation have been found to differ. Although not completely delineated, UVB radiation-induced modulation of ICAM-1 expression appears to be mediated via the induction of DNA damage, whereas UVA1 radiation effects involve the generation of reactive oxygen intermediates.
authors.affiliation: Department of Dermatology, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Krutmann
authors.forename: M
authors.initials: M
authors.lastname: Grewe
mesh_terms: D000818:Animals; D016207:Cytokines / Q000502:physiology*; D004249:DNA Damage; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism; D018462:Photobiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; D018799:Intercellular Adhesion Molecule-1