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섬유아세포에서 자외선 노출후 생성된 Inflammatory cytokines과 금속단백분해효소에 대한 Interleukin-4와 Interleukin-10의 억제효과
Currently, we receive a greater lifetime exposure to ultraviolet radiation due to increased UV reaching the earth's surface. Chronic exposure to UV irradiation is associated with severe external eye disease, squamous metaplasia and age related macular degeneration. This response to UV exposure appear to be mediated by the release of cytokines such as IL1, IL6, IL8 and tumor necrosis factor-α (TNF-α). On the other hand, IL4 and IL10 are known as immunomodulatory cytokines and expected to be potential therapeutic agents in certain inflammatory diseases due to their suppressive effects of inflammatory reaction. The purpose of this study is to evaluate the effects of IL4, IL10 on the expression of inflammatory cytokines and metalloproteinases in cultured normal human dermal fibroblasts following UVB (312 nm) irradiation. We examined the changes of the viability of the cultured normal human dermal fibroblast (NHDF) at 1, 3, 5 minutes following UVB irradiation. TNF-α and IL-1β mRNA expression from NHDF following UVB irradiation was determined by reverse transcriptase polymerase chain reaction (RT-PCR) and quantified by densitometer. MMP-1, MMP-3 concentration after UVB exposure was measured by ELISA. After the cells were treated with various concentrations of IL4, IL10, IL4 + IL10 (0.5-50 ng/ml) and irradiated with UVB for 5minutes, we examined the changes of TNF-α, IL-1β mRNA in NHDF and MMP-1, MMP-3 in culture media. There were no statistically significant changes of the cell viability at 1, 3, 5 minutes following UVB irradiation. TNF-α and IL1β expressions were up-regulated at 3 minutes and 5 minutes of UVB exposure. TNF-α and IL-1β expression was inhibited at all concentrations of IL4, IL10, IL4 + IL10 (0.5-50 ng/ml) which was treated before UVB irradiation. The inhibitory effects were decreased when the concentrations were increased. MMP-1 and MMP-3 production decreased significantly at all concentrations of IL4, IL10 and IL4 + IL10 in dose dependent manner. Furthermore, the maximal inhibitory effect was achieved at 50 ng/ml of IL4 + IL10. In conclusion, we proved that UVB is a potent inducer of inflammatory cytokines such as TNF-α and IL-1β. IL4 and IL10 down-regulated these cytokines, suppressed the production of MMP-1, MMP-3.