School of Medical Sciences, RMIT University, PO Box 71, Bundoora VIC 3083, Australia.
Int J Mol Sci. 2013 Aug 19;14(8):17029-54. doi: 10.3390/ijms140817029.
Ultraviolet (UV) radiation activates cell signaling pathways in melanocytes. As a result of altered signaling pathways and UV-induced cellular damage, melanocytes can undergo oncogenesis and develop into melanomas. In this study, we investigated the effect of UV-radiation on p38 MAPK (mitogen-activated protein kinase), JNK and NFκB pathways to determine which plays a major role in stimulating TNFα secretion in human HEM (melanocytes) and MM96L (melanoma) cells. MM96L cells exhibited 3.5-fold higher p38 activity than HEM cells at 5 min following UVA + B radiation and 1.6-fold higher JNK activity at 15-30 min following UVB+A radiation, while NFκB was minimally activated in both cells. Irradiated HEM cells had the greatest fold of TNFα secretion (UVB: 109-fold, UVA + B: 103-fold & UVB+A: 130-fold) when co-exposed to IL1α. The p38 inhibitor, SB202190, inhibited TNFα release by 93% from UVB-irradiated HEM cells. In the UVB-irradiated MM96L cells, both SB202190 and sulfasalazine (NFκB inhibitor) inhibited TNFα release by 52%. Although, anisomycin was a p38 MAPK activator, it inhibited TNFα release in UV-irradiated cells. This suggests that UV-mediated TNFα release may occur via different p38 pathway intermediates compared to those stimulated by anisomycin. As such, further studies into the functional role p38 MAPK plays in regulating TNFα release in UV-irradiated melanocyte-derived cells are warranted.
紫外线（UV）辐射激活黑素细胞中的细胞信号通路。由于信号通路改变和 UV 诱导的细胞损伤，黑素细胞可能发生癌变并发展为黑色素瘤。在这项研究中，我们研究了 UV 辐射对 p38 MAPK（丝裂原活化蛋白激酶）、JNK 和 NFκB 通路的影响，以确定哪些通路在刺激人 HEM（黑素细胞）和 MM96L（黑色素瘤）细胞中 TNFα 的分泌中起主要作用。在 UVA+B 辐射后 5 分钟，MM96L 细胞中的 p38 活性比 HEM 细胞高 3.5 倍，在 UVB+A 辐射后 15-30 分钟，JNK 活性高 1.6 倍，而 NFκB 在两种细胞中的激活程度较低。当与 IL1α 共暴露时，辐照的 HEM 细胞的 TNFα 分泌倍数最大（UVB：109 倍，UVA+B：103 倍和 UVB+A：130 倍）。p38 抑制剂 SB202190 抑制 UVB 辐照的 HEM 细胞中 TNFα 释放 93%。在 UVB 辐照的 MM96L 细胞中，SB202190 和柳氮磺胺吡啶（NFκB 抑制剂）均抑制 TNFα 释放 52%。尽管anisomycin 是 p38 MAPK 激活剂，但它抑制了 UV 照射细胞中 TNFα 的释放。这表明与 anisomycin 刺激的相比，UV 介导的 TNFα 释放可能通过不同的 p38 通路中间产物发生。因此，有必要进一步研究 p38 MAPK 在调节 UV 照射的黑素细胞衍生细胞中 TNFα 释放中的功能作用。
