INTERLEUKIN-8 STIMULATES CALCIUM TRANSIENTS AND PROMOTES EPIDERMAL-CELL PROLIFERATION

INTERLEUKIN-8 STIMULATES CALCIUM TRANSIENTS AND PROMOTES EPIDERMAL-CELL PROLIFERATION
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DOI:
10.1111/1523-1747.ep12616634
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发表时间:
1992-09-01
影响因子:
6.5
通讯作者:
LINDLEY, I
LINDLEY, I
中科院分区:
医学1区
文献类型:
--
作者:
TUSCHIL, A;LAM, C;LINDLEY, I

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银屑病累及皮肤中存在大量具有生物活性的白细胞介素-8(IL-8),这表明它可能部分导致银屑病中观察到的变化,包括角质形成细胞过度增殖。为了检测IL-8对表皮生长的影响,我们监测了人角质形成细胞中细胞溶质游离Ca++瞬变,成人皮肤表皮钙降低水平,温度升高(HaCat)细胞和加载有细胞可渗透的乙酰氧基甲基衍生物indo-1AM的正常角质形成细胞。向HaCat细胞中加入IL-8(0.06 - 47 nM)诱导胞质游离Ca++从145 +/- 38的静息水平快速升高至889 +/- 10 nM的峰值水平。诱导的Ca++升高是短暂的和浓度依赖性的。在1.2 nM下观察到半数最大效应。正常角质形成细胞也响应于IL-8(6 nM),胞质游离Ca++从269 nM的预刺激水平升高至393 nM的瞬时峰值。此外,IL-8促进表皮细胞增殖。多克隆抗IL-8抗体阻断IL-8诱导的钙变化和增殖。在相似的条件下,人中性粒细胞也响应于IL-8在相似的剂量范围内通过快速和短暂的动员Ca++。研究结果表明,IL-8具有比迄今为止认为的更广泛的响应靶细胞,并作为自分泌生长因子。
The presence of large amounts of biologically active interleukin-8 (IL-8) in psoriatic involved skin suggests that it may contribute, in part, to the changes observed in psoriasis, including hyperproliferation of keratinocytes. To examine the effect of IL-8 on epidermal growth, we monitored cytosolic free Ca++ transients in human keratinocytes adult skin epidermis calcium reduced level, temperature elevated (HaCat) cells and normal keratinocytes loaded with the cell permeable, acetoxymethyl derivative, indo-1AM. Addition of IL-8 (0.06 - 47 nM) to the HaCat cells induced rapid rises in cytosolic free Ca++ from resting levels of 145 +/- 38 to peak levels of 889 +/- 10 nM. The induced rises in Ca++ were transient and concentration dependent. Half maximal effect was observed at 1.2 nM. Normal keratinocytes also responded to IL-8 (6 nM) by rises in cytosolic free Ca++ from a pre-stimulated level of 269 nM to transient peak value of 393 nM. In addition, IL-8 promoted epidermal cell proliferation. Polyclonal anti-IL-8 antibody blocked IL-8-induced calcium changes and proliferation. Under similar conditions, human neutrophils also responded to IL-8 in a similar dose range by a rapid and transient mobilization of Ca++. The findings indicate that IL-8 has a wider range of responsive target cells than hitherto thought and acts as an autocrine growth factor.