Modulation of IL-10, IL-12, and IFN-γ in the Epidermis of Hairless Mice by UVA (320–400 nm) and UVB (280–320 nm) Radiation

Abstract

We have observed recently that the suppression of contact hypersensitivity (CHS) induced in mice by UVB irradiation may be prevented by suberythemal exposure to UVA radiation. Because the UVB-immunosuppressed state is associated with an upregulation of the Th2-associated cytokines IL-10 and IL-4, and a deficiency in Th1-associated IL-2, IL-12, and IFN-gamma, and because UVA photoimmunoprotection appeared to be IFN-gamma- dependent, we tested the hypothesis that UVA immunoprotection results from an ability to prevent the UVB-induced cytokine disarray. This study describes changes in epidermal IL-10, IL-12 and IFN-gamma for 5 d following irradiation of hairless mice with the CHS-modulating doses of UVB, UVA, or UVA + UVB, using immuno-histochemical detection in paraffin embedded skin sections, followed by image analysis quantitation. We found that UVB, but not UVA exposure, caused an increase in epidermal IL-10 expression, peaking at 3 d. UVA irradiation, but not UVB, resulted in increased epidermal IL-12 expression, peaking at 3 d, and increased epidermal IFN-gamma expression peaking earlier at 1 d. Irradiation with UVA + UVB abrogated the UVB-enhanced expression of IL-10, and caused small but significant increases in IL-12 and IFN-gamma at 3 d and 1 d, respectively. These findings suggest that UVA photoimmunoprotection is mediated via prevention of IL-10 release, and thus the maintenance of the Th1/Th2 balance, probably by upregulation of IL-12 and IFN-gamma, which are known to antagonize IL-10 in numerous models. The time course suggests that IFN-gamma responds initially to UVA radiation, and may stimulate the increased expression of IL-12.

UVA and UVB wavebands modulate expression ofFasLin mouse skin epidermis

“…Irradiation with UVA, which we know to protect the mouse from UVB-immunosuppression, significantly reduced UVB-induced FasL expression. This result may indicate that UVA immunoprotection against UVB may result not only from the up-regulation of immunoprotective Th1 cytokines in the epidermis as our previous study suggested, 2 but also from the maintenance of the cutaneous immune balance via the Fas/FasL system. Thus the reduced presence of IFN-γ and the enhanced expression of FasL in the UVB-irradiated epidermis, both indicators of immunosuppression, have been reversed by the immunoprotective UVA irradiation.…”

“…1 We observed different cytokine modulation in mouse epidermis by the UVA and UVB wavebands: UVA acts as an inducer of Th1-derived cytokines like IL-12 and IFN-γ, while UVB is responsible for induction of Th2-derived cytokines like IL-10, a major cause of immunosuppression. 2 However, the underlying mechanism(s) by which UVA achieved immunoprotection against UVB have remained undefined. Recently, much attention has focused on the apoptosis process during immune responses to UV irradiation, in which the Fas/FasL system has been reported to play a major role.…”

Reconstituted High-Density Lipoproteins Inhibit the Acute Pro-Oxidant and Proinflammatory Vascular Changes Induced by a Periarterial Collar in Normocholesterolemic Rabbits

“…Digital micrographs were acquired with an Olympus BX40 microscope, and the percentage of total vessel wall area occupied by positive staining was determined by use of ImagePro Plus 4 (Cybernetics). 24 …”

The pathophysiology of photosensitivity in lupus erythematosus

“…UVA exposure also results in a rapid increase in interferon-g (IFN-g) levels in the skin, the source of which may be resident epidermal T cells (232). Elevated IFN-g mRNA levels are noted in lesions of cutaneous LE (234).…”