PRESENCE OF EPIDERMAL-DERIVED THYMOCYTE ACTIVATING FACTOR INTERLEUKIN-1 IN NORMAL HUMAN STRATUM-CORNEUM

PRESENCE OF EPIDERMAL-DERIVED THYMOCYTE ACTIVATING FACTOR INTERLEUKIN-1 IN NORMAL HUMAN STRATUM-CORNEUM
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DOI:
10.1172/jci112141
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发表时间:
1985-01-01
影响因子:
15.9
通讯作者:
DAYNES, RA
DAYNES, RA
中科院分区:
医学1区
文献类型:
--
作者:
GAHRING, LC;BUCKLEY, A;DAYNES, RA

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角化细胞产生一种分子,表皮源性胸腺细胞活化因子(ETAF),它在生物学和物理化学上与多肽激素白介素1 (IL-1)相似。由于角质层(SC)由终末分化的角质形成细胞组成,我们质疑能否从该组织中分离出ETAF/IL-1。通过体外胸腺细胞共刺激试验,用生理盐水溶液提取正常人SC可产生大量的ETAF/IL-1活性。sc衍生的ETAF/IL-1 (scETAF/IL-1)从分子量约为15,000的上浆柱中洗脱,在色谱聚焦柱上分离后显示出三种等电点形式。通过这些物理化学特征,发现scETAF/IL-1与人角质形成细胞和巨噬细胞来源的ETAF/IL-1相似,如果不是完全相同的话。此外,一些已知的生物效应在给药ETAF/IL-1后会在体内发生,如发热、中性粒细胞增多和血浆急性期蛋白水平升高,这些都是通过向内毒素无反应的小鼠注射scETAF/IL-1诱导的。scETAF/IL-1也被发现在体外刺激人成纤维细胞产生胶原酶。综上所述,我们的研究已经确定正常人类SC中含有大量的scETAF/IL-1。scETAF/IL-1是否整合到局部炎症反应的最早传入阶段,或者仅仅代表一种处理过量产生的激素的手段,目前尚不清楚。
Keratinocytes produce a molecule, epidermal-derived thymocyte activating factor (ETAF), which is biologically and physiochemically similar to the polypeptide hormone interleukin 1 (IL-1). Because the stratum corneum (SC) is composed of terminally differentiated keratinocytes, we questioned whether ETAF/IL-1 could be isolated from this tissue. The extraction of normal human SC with a physiologic saline solution yielded a large amount of ETAF/IL-1 activity, as measured by the in vitro thymocyte co-stimulator assay. SC-derived ETAF/IL-1 (scETAF/IL-1) eluted from a sizing column with an approximate molecular weight of 15,000, and demonstrated three isoelectric point forms after separation on a chromatofocusing column. By these physiochemical characteristics, scETAF/IL-1 was found to be similar, if not identical to human keratinocyte- and macrophage-derived ETAF/IL-1. Further, a number of biologic effects known to occur in vivo after the administration of ETAF/IL-1, such as fever, neutrophilia, and an increase in plasma levels of acute-phase proteins, were all induced by the injection of scETAF/IL-1 into endotoxin-nonresponsive mice. scETAF/IL-1 was also found to stimulate collagenase production by human fibroblasts in vitro. In summary, our studies have established that normal human SC contains a large quantity of scETAF/IL-1. Whether scETAF/IL-1 integrates into the earliest afferents phases of local inflammatory responses, or merely represents a means of disposal of excessively produced hormone is currently unresolved.