Induction of Interleukin-6 Production by Ultraviolet Radiation in Normal Human Epidermal Keratinocytes and in a Human Keratinocyte Cell Line is Mediated by DNA Damage

Abstract

The sunburn reaction is the most common consequence of human exposure to ultraviolet radiation (UVR), and is mediated at least in part by interleukin-6 (IL-6). The aim of this study was to determine if DNA is a major chromophore involved in the induction of IL-6 following UV irradiation of a human epidermoid carcinoma cell line (KB), and of normal human epidermal keratinocytes. We first confirmed that IL-6 release was associated with enhanced levels of IL-6 mRNA transcripts. The wavelength dependence for IL-6 release was then investigated by irradiating the cells at defined wavelengths (254, 302, 313, 334, and 365 nm) with a monochromator. The maximum effect on IL-6 release was observed at 254 nm with only low levels of induction observed at wavelengths above 313 nm. The wavelength dependence for UV-induced IL-6 release was similar to that for DNA absorption or for the induction of cyclobutane pyrimidine dimers (CPD). To determine whether UV-induced DNA damage mediated IL-6 secretion, the role of CPD was investigated by treating keratinocytes with photosomes (photolyase encapsulated in liposomes) followed by photoreactivating light. This photoreversal procedure led to a reduction in the levels of the UVC-induced secretion of IL-6, which in normal human keratinocytes was unambiguously associated with repair of CPD. We conclude that the release of IL-6 from human keratinocytes following short-wave UVC and UVB irradiation is mediated by DNA damage and that CPD play an important role in this process.

Ultraviolet Radiation-induced Interleukin 6 Release in HeLa Cells Is Mediated via Membrane Events in a DNA Damage-independent Way

“…In contrast to UV-induced apoptosis, UV-mediated IL-6 release by HeLa cells was not affected at all by accelerated removal of pyrimidine dimers. These observations are in contrast to a recent publication by Petit-Frere et al (9), in which they reported that photoreactivation led to a reduction of IL-6 release in KB cells and normal human keratinocytes. However, in that case inhibition of UVinduced IL-6 release was not complete, implying that other pathways may be involved as well.…”

“…porphyrins, aromatic amino acids, urocanic acid, and DNA. Among these, DNA has been regarded as the most important one, since the wavelength dependences of various UV effects match that of DNA absorption (9). In addition, removal of UV-induced DNA damage, e.g.…”

Differential modulation of inflammatory markers in plasma and skin after single exposures to UVA or UVB radiation in vivo

“…Both foregoing cytokines, IL-1 and TNF-α stimulate production of pleiotropic IL-6. Petit-Frère et al also showed that release of IL-6 following UV radiation is wavelengthdependent and mediated by DNA damage, particularly by cyclobutane-pyrimidine dimmers 21 . Using a solar simulator, we found a different time-course of plasma IL-6 production after UVA and UVB treatment.…”

UVA‐1 exposure in vivo leads to an IL‐6 surge within the skin

“…[10] Given this fact, it seems at first not likely that UVA-1 might be capable of a significant IL-6 induction in vivo. However, recent work by Tewari et al [11] in vivo has demonstrated the capability of UVA-1 to also induce CPD in significant amounts.…”

“…Thus, the DNA damage-related mechanism of IL-6 release was shown to exist also for the UVA-1 spectrum in vivo and this fits with our data. [10] The IL-6 release in vivo has been suggested by several in vitro studies in the past with keratinocytes and…”