Hammerberg C, Bata-Csorgo Z, Voorhees J J, Cooper K D
Department of Dermatology, University Hospitals of Cleveland, Case Western Reserve University, OH 44106-4962, USA.
Arch Dermatol Res. 1998 Jul;290(7):367-74. doi: 10.1007/s004030050319.
Changes in the levels of IL-1 (IL-1alpha, IL-1beta, and its receptor antagonist, IL-1RA) occur upon keratinocyte differentiation in vitro and are associated in vivo with abnormal differentiated and hyperproliferative states of psoriatic keratinocytes. A flow cytometric procedure, capable of detecting changes in the intracellular levels of IL-1, was used to determine whether intracellular IL-1/IL-1RA levels in psoriatic and normal keratinocytes alter during in vivo differentiation and the cell cycle. Increases in the IL-1RA levels and IL-1alpha levels were observed as both normal and psoriatic keratinocytes differentiated from basal stem cells (beta1 integrin+, small size) into transient amplifying cells (TAC; beta1 integrin+, large size). Upon further differentiation (beta1 integrin-, large size) both IL-1RA and IL-1alpha levels dropped. However, while psoriatic IL-1beta levels increased as cells differentiated into TACs, little change occurred in the IL-1beta levels of normal keratinocytes during differentiation. Changes in IL-1/IL-1RA levels were also detected as keratinocytes progressed through the cell cycle. Within the basal stem cell population of both normal and psoriatic keratinocytes, the IL-1alpha and IL-1RA levels increased between G0/G1 and S but not between S and G2/M. However, psoriatic basal keratinocyte IL-1beta levels differed from those of normal keratinocytes by showing no increase between S and G2/M. The IL-1/IL-1RA levels of normal TAC increased throughout the cell cycle. However, in psoriatic TAC, a slight decrease in IL-1alpha and IL-1RA levels was observed between G0/G1 and S followed by a delayed increase between S and G2/M. IL-1beta levels in psoriatic TAC varied little throughout the cell cycle. Thus, we were able to detect precisely the regulation of IL-1/IL-1RA intracellular levels during the keratinocyte cell cycle and differentiation, showing notably decreased IL-1beta upregulation in psoriatic keratinocytes progressing through the cell cycle.
白细胞介素-1（IL-1，包括IL-1α、IL-1β及其受体拮抗剂IL-1RA）水平的变化在体外角质形成细胞分化时出现，并且在体内与银屑病角质形成细胞的异常分化和增殖过度状态相关。一种能够检测细胞内IL-1水平变化的流式细胞术程序，被用于确定银屑病和正常角质形成细胞在体内分化和细胞周期过程中细胞内IL-1/IL-1RA水平是否改变。当正常和银屑病角质形成细胞从基底干细胞（β1整合素阳性，小尺寸）分化为短暂增殖细胞（TAC；β1整合素阳性，大尺寸）时，观察到IL-1RA水平和IL-1α水平升高。在进一步分化（β1整合素阴性，大尺寸）时，IL-1RA和IL-1α水平均下降。然而，当细胞分化为TAC时，银屑病IL-1β水平升高，而正常角质形成细胞在分化过程中IL-1β水平变化不大。随着角质形成细胞经历细胞周期，也检测到了IL-1/IL-1RA水平的变化。在正常和银屑病角质形成细胞的基底干细胞群体中，IL-1α和IL-1RA水平在G0/G1期和S期之间升高，但在S期和G2/M期之间没有升高。然而，银屑病基底角质形成细胞的IL-1β水平与正常角质形成细胞不同，在S期和G2/M期之间没有升高。正常TAC的IL-1/IL-1RA水平在整个细胞周期中升高。然而，在银屑病TAC中，在G0/G1期和S期之间观察到IL-1α和IL-1RA水平略有下降，随后在S期和G2/M期之间延迟升高。银屑病TAC中的IL-1β水平在整个细胞周期中变化不大。因此，我们能够精确检测角质形成细胞周期和分化过程中IL-1/IL-1RA细胞内水平的调节，显示在经历细胞周期的银屑病角质形成细胞中IL-1β上调明显减少。
