UVA and UVB induce distinct sets of inflammatory mediators and, therefore, have different impacts on the immune and inflammatory responses (O'Garra and Murphy 1993). First, UVA and UVB increase levels of both interleukin (IL)-10 and IL-12,but the levels induced differ, with UVB producing more IL-10 than UVA and UVA1 producing more IL-12 than UVB (Kondo and Jimbow 1998, Skov et al. 1997, Werth et al. 2003). IL-10 produced from irradiated keratinocytes induces systemic immunosuppression and tolerance by promoting the Th2 response (Rivas and Ullrich 1992), whereas IL-12 seems to promote a Th1 response (Adorini 1999). IL-12 can reverse UV-induced IL-10 immunosuppression and tolerance (Schmitt et al. 1995, Schwarz et al. 1996), either by inhibiting Th2 cells from secretion of IL-4 and IL-10 (Schmitt et al. 1995) or by blocking IL-10 and tumor necrosis factor (TNF)-a release at the level of the keratinocyte (Schmitt et al. 2000,Werth et al. 2003). IL-10 and TNF-a likely have different roles in UV-induced immunosuppression and tolerance, with TNF-a involved in the induction of immune suppression and IL-10 involved in tolerance (Niizeki and Streilein 1997).
Second, UV induces IL-1a and TNF-a, which leads to increased expression of adhesion molecules on keratinocytes and endothelial cells, which causes local recruitment of inflammatory cells (Bennion et al. 1995, Dorner et al. 1995b, Heckmann et al. 1994). The importance of adhesion molecules in the pathogenesis of photosensitive disease is demonstrated by the fact that there is increased expression of intercellular adhesion molecule-1 (ICAM-1), histocompatibility class II molecules (HLA-DR), E-selectin, and vascular cell adhesion molecule-1 (VCAM-1) in lesional skin of patients with SCLE, DLE, or LET compared with controls (Hausmann et al. 1996, Kuhn et al. 2002). Soluble E-selectin is increased in CLE (Kubo et al. 2000), as is soluble ICAM-1 (Kumamoto et al. 1997) and soluble VCAM-1. Finally, MRL/lpr mice have an exaggerated ICAM-1-dependent leukocyte endothelial interaction, which may contribute to increased inflammation in this murine model of LE (Marshall et al. 2003).
Third, UVB modifies the production of the chemokines CXCL1 and CXCL2 (Kondo et al. 2000), whereas UVA inhibits chemokine CCL17 production from keratinocytes (Zheng et al. 2003). CXCR3-activating chemokines (CXCL9, CXCL10, and CXCL11), as well as HLA-DR3 and ICAM-1, are preferentially expressed at the dermal-epidermal junction and periadnexal areas in DLE lesional skin. CD4+ and CD8+ dermal T cells are located in the same areas that express the CXCR3 receptor, suggesting that these chemokines may have an effect on leukocyte recruitment. Interferon (IFN)-y induces keratinocyte and macrophage expression of chemokines, HLA-DR3, and ICAM-1, suggesting that IFN-y has an important immunomodulatory role in DLE (Flier et al. 2001). Low levels of IFN-y are associated with a reduced autoantibody response in murine lupus models (Pollard 2002).
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