Schwarz A, Mahnke K, Luger T A, Schwarz T
Ludwig Boltzmann Institute for Cellbiology and Immunobiology of the Skin, Department of Dermatology, University Münster, Germany.
Exp Dermatol. 1997 Feb;6(1):1-5. doi: 10.1111/j.1600-0625.1997.tb00138.x.
Irradiation with ultraviolet (UV) B light results in the formation of apoptotic keratinocytes called sunburn cells (SC). Although generation of SC appears to be one of the most characteristic features of UV-induced skin damage and has been a well-known phenomenon for a long time, the mechanisms involved are not quite clear. Recently, it was demonstrated that tumor necrosis factor alpha (TNF alpha) appears to be involved in the formation of SC since neutralization of TNF alpha both in vitro and in vivo reduced UVB-induced apoptosis of keratinocytes. Pentoxifylline is a methylxanthine derivative suppressing the release of TNF alpha. Therefore, we studied whether PTX is able to prevent the formation of SC. Addition of PTX to UVB-exposed HaCaT cells reduced DNA-fragmentation as examined by nick translation evaluated by flowcytometry. To prove whether PTX also reduces UVB-induced apoptosis in vivo, BALB/c mice were exposed to UVB on their abdomens, skin biopsies performed 24 h later and SC counted. A single dose of 2000 J/m2 caused a significant induction of SC which were remarkably reduced when PTX was injected intraperitoneally 3 h before and 12 h after UVB exposure. In summary, the data demonstrate that PTX can reduce the formation of SC both in vitro and in vivo and thus further support that TNF alpha is involved in UVB-induced apoptosis of keratinocytes.
用紫外线B(UVB)照射会导致形成一种称为晒伤细胞(SC)的凋亡角质形成细胞。虽然晒伤细胞的产生似乎是紫外线诱导皮肤损伤最具特征性的表现之一,且长期以来一直是一个广为人知的现象,但其中涉及的机制尚不完全清楚。最近,有研究表明肿瘤坏死因子α(TNFα)似乎参与了晒伤细胞的形成,因为在体外和体内对TNFα进行中和都能减少UVB诱导的角质形成细胞凋亡。己酮可可碱是一种抑制TNFα释放的甲基黄嘌呤衍生物。因此,我们研究了己酮可可碱是否能够预防晒伤细胞的形成。通过流式细胞术评估缺口平移检测发现,向暴露于UVB的HaCaT细胞中添加己酮可可碱可减少DNA片段化。为了证明己酮可可碱在体内是否也能减少UVB诱导的凋亡,将BALB/c小鼠腹部暴露于UVB,24小时后进行皮肤活检并计数晒伤细胞。2000 J/m2的单剂量UVB照射可显著诱导晒伤细胞的产生,而在UVB照射前3小时和照射后12小时腹腔注射己酮可可碱时,晒伤细胞的数量会显著减少。总之,这些数据表明己酮可可碱在体外和体内均可减少晒伤细胞的形成,从而进一步支持TNFα参与UVB诱导的角质形成细胞凋亡这一观点。