| Popis: |
Depletion of stratospheric ozone and changes in lifestyles have led to increased concern about the harmful effects of ultraviolet radiation (UVR). Exposure to UVR has been shown to induce both local and systemic suppression of immune responses initiated through the skin. The mechanism of dysregulation of immune responses following UV exposure is complex, and is initiated by chromophores. One such chromophore is urocanic acid (UCA), which is isomerised from the trans- to the cis-isoform by UVR, in the epidermis. The primary antigen presenting cell (APC) of the skin, the Langerhans cell (LC), plays a critical role in cutaneous immune responses. UVR alters LC frequency within the irradiated epidermis, and also exerts effects on the mature form of LC, the dendritic cells (DC), within lymph nodes draining irradiated sites. These changes appear to be concurrent with an alteration in T cell cytokine profiles. UVR suppresses immune responses which are normally characterised by Th1 -like cytokine profiles, possibly by immune deviation to Th2 -like cytokine profiles. The contact hypersensitivity (CH) response is commonly used to demonstrate cutaneous immunity. A model of CH in C3H/HeN mice was established. This model was utilised to examine the effects of local UVB irradiation before induction of contact sensitisation. Cytokine profiles within lymph nodes draining the site of elicitation of CH, or the site of contact sensitisation were investigated. Results suggest that UVB has no effect on cytokine production during the sensitisation phase of CH, but that it downregulates Th1 -like cytokine production upon elicitation of CH. Effects of UVR and UCA application were examined in relation to LC frequency within the epidermis. UVA1 (340- 400nm) irradiation, or trans-UCA application, did not alter the LC numbers within the exposed site. UVB (280-315nm) irradiation and cis-UCA application depleted LC, and timecourses for LC depletion were established for both treatments. Injection of antibodies against either IL-1ß or TNF-α before UVB irradiation or cis-UCA treatment completely abrogated their effects on LC numbers. Thus, the UVB-mediated reduction of LC is dependent on the cytokines IL-1P and TNF-α. Despite reports that UVA1 irradiation protects mice from subsequent immunosuppression by UVB exposure, UVA1 irradiation did not affect the decrease in LC numbers induced by UVB. Despite the differences in effects on LC frequency, both UVA1 and UVB induced an accumulation of DC within lymph nodes draining the site of irradiation. For both irradiation regimens, the accumulation of DC was dependent on IL-1ß. This was identified by injecting neutralising IL-1ß antibodies before irradiation, which inhibited the accumulation of DC within draining lymph nodes following irradiation. Similar experiments indicated that accumulation of DC following UVB irradiation, but not following UVA1 irradiation, was also dependent upon TNF-α. Induction of cytokines within irradiated skin was examined. UVB exposure increased the expression of IL-10 and TNF-α proteins at the irradiated site. Attempts to identify the source of these cytokines were inconclusive, as both keratinocyte (PAM-212) and melanocyte (B16) cell lines failed to secrete these cytokines following UVB irradiation. Intracellular stores of TNF-α decreased as the dose of radiation increased. The technique of reverse transcription polymerase chain reaction (RT -PCR) was established to examine expression of cytokine mRNA in irradiated skin. Following UVB irradiation, TNF -a mRNA was upregulated and there was induction of IL-10 mRNA. UVA1 irradiation did not result in such changes. There were also differences in the timecourse of IL-1ß mRNA upregulation. IL-1ß mRNA expression peaked transiently 4h after UVB irradiation. Following UVA1 irradiation, IL-1ß mRNA expression did not peak until 24h, and remained upregulated at 48h, after exposure. |
