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白细胞介素-6细胞因子家族成员制瘤素M是一种在毛囊中表达的具有毛发生长抑制特性的因子。

Interleukin-6 cytokine family member oncostatin M is a hair-follicle-expressed factor with hair growth inhibitory properties.

作者信息

Yu Mei, Kissling Sabine, Freyschmidt-Paul Pia, Hoffmann Rolf, Shapiro Jerry, McElwee Kevin J

机构信息

Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.

出版信息

Exp Dermatol. 2008 Jan;17(1):12-9. doi: 10.1111/j.1600-0625.2007.00643.x. Epub 2007 Nov 2.

Abstract

The activation of receptor complexes containing glycoprotein 130 (gp130) identifies the interleukin (IL)-6 cytokine family. We examined members of this family for their expression and activity in hair follicles. Quantitative polymerase chain reaction using mRNA derived from microdissected, anagen-stage human hair follicles and comparison to non-follicular skin epithelium revealed higher levels of IL-6 (15.5-fold) and oncostatin M (OSM, 3.4-fold) in hair follicles. In contrast, expression of all mRNAs coding for IL-6 cytokine family receptors was reduced. Immunohistology suggested expression of OSM, gp130, leukaemia inhibitory factor receptor (LIFr) and IL-11r in the hair follicle root sheaths and dermal papilla, while IL-11, IL-6r and OSMr were expressed in root sheaths alone. IL-6 was expressed in the dermal papilla while cardiotrophin-1 (CT-1) and LIF were not observed. OSM and to a lesser extent CT-1 exhibited a dose-dependent growth inhibition capacity on human hair follicles in vitro. OSM and CT-1 incubated with agarose beads and injected subcutaneously at 1 mug per mouse into telogen skin of 65-day-old mice revealed no capacity to induce anagen hair growth. In contrast, injection of 65-day-old mice in which anagen had been induced by hair plucking revealed a moderate hair growth inhibitory capacity for OSM, but no significant effect for CT-1. The data identify OSM as a modulator of hair follicle growth and suggest other family members may also have some degree of hair growth inhibitory effect. In principle, increased expression of some IL-6 cytokine family members in cutaneous inflammation might contribute to the promotion of hair loss.

摘要

含有糖蛋白130(gp130)的受体复合物的激活可识别白细胞介素(IL)-6细胞因子家族。我们研究了该家族成员在毛囊中的表达和活性。使用来自显微切割的生长期人毛囊的mRNA进行定量聚合酶链反应,并与非毛囊皮肤上皮进行比较,结果显示毛囊中IL-6(15.5倍)和抑瘤素M(OSM,3.4倍)的水平更高。相比之下,编码IL-6细胞因子家族受体的所有mRNA的表达均降低。免疫组织学表明,OSM、gp130、白血病抑制因子受体(LIFr)和IL-11r在毛囊根鞘和真皮乳头中表达,而IL-11、IL-6r和OSMr仅在根鞘中表达。IL-6在真皮乳头中表达,而未观察到心肌营养素-1(CT-1)和LIF。OSM以及程度较轻的CT-1在体外对人毛囊表现出剂量依赖性的生长抑制能力。将OSM和CT-1与琼脂糖珠一起孵育,并以每只小鼠1微克的剂量皮下注射到65日龄小鼠的休止期皮肤中,结果显示没有诱导生长期毛发生长的能力。相比之下,对通过拔毛诱导进入生长期的65日龄小鼠进行注射,结果显示OSM具有中等程度的毛发生长抑制能力,但CT-1没有显著作用。这些数据确定OSM是毛囊生长的调节剂,并表明其他家族成员可能也具有一定程度的毛发生长抑制作用。原则上,皮肤炎症中一些IL-6细胞因子家族成员表达的增加可能有助于促进脱发。

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