Mandt Nathalie, Geilen Christoph C, Wrobel Anna, Gelber Alexandra, Kamp Hartwig, Orfanos Constantin E, Blume-Peytavi Ulrike
Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, Fabeckstr. 60-62, 14195 Berlin, Germany.
Eur J Dermatol. 2002 Sep-Oct;12(5):432-8.
The importance of apoptosis in hair follicle cycling is still not clearly understood, however, its regulation in follicular keratinocytes (FK) during bulb regression (catagen) may be essential for hair regrowth. So far, the control of FK apoptosis remains unknown. In this study, the anti-inflammatory cytokine IL-4 was found to induce apoptosis dose and time dependently in cultured human FK, in contrast to other agents known to inhibit hair growth such as IL-1alpha, IL-1beta, TNFalpha and TGFbeta, as shown by DNA fragmentation. On the other hand, cytokines reported to be involved in hair follicle cycling including IL-4 were not able to induce apoptosis in dermal papilla cells (DPC), in contrast to staurosporine. This PKC inhibitor revealed dose-dependent apoptotic signals not only for DPC but also for FK in vitro. In further experiments the expression of apoptosis regulating proteins, possibly involved in catagen formation, was analyzed in FK and DPC. However, no striking difference in RNA expression was seen in either cell population under culture conditions and after incubation with IL-4. We conclude, therefore, that IL-4 mediated apoptosis may participate in regulating catagen formation in the hair follicle, acting selectively on cultured FK and being independent of bcl-2 and bax expression.
细胞凋亡在毛囊周期中的重要性仍未被完全理解,然而,其在球部退化(退行期)期间对毛囊角质形成细胞(FK)的调节可能对毛发再生至关重要。到目前为止,FK细胞凋亡的调控机制仍不清楚。在本研究中,与其他已知抑制头发生长的因子如IL-1α、IL-1β、TNFα和TGFβ不同,抗炎细胞因子IL-4被发现可在培养的人FK中剂量和时间依赖性地诱导细胞凋亡,DNA片段化结果表明了这一点。另一方面,与星形孢菌素不同,包括IL-4在内的据报道参与毛囊周期的细胞因子不能在真皮乳头细胞(DPC)中诱导细胞凋亡。这种蛋白激酶C抑制剂不仅在体外对DPC而且对FK都显示出剂量依赖性的凋亡信号。在进一步的实验中,分析了可能参与退行期形成的凋亡调节蛋白在FK和DPC中的表达。然而,在培养条件下以及与IL-4孵育后,在这两种细胞群体中均未观察到RNA表达的显著差异。因此,我们得出结论,IL-4介导的细胞凋亡可能参与调节毛囊中的退行期形成,选择性地作用于培养的FK,且与bcl-2和bax表达无关。