培养的角质形成细胞和成纤维细胞中年龄与促黑素细胞细胞因子分泌之间的相关性。

Correlation between age and the secretions of melanocyte-stimulating cytokines in cultured keratinocytes and fibroblasts.

作者信息

Okazaki M, Yoshimura K, Uchida G, Harii K

机构信息

Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

出版信息

Br J Dermatol. 2005 Dec;153 Suppl 2:23-9. doi: 10.1111/j.1365-2133.2005.06966.x.

DOI:10.1111/j.1365-2133.2005.06966.x

PMID:16280018

Abstract

BACKGROUND

The majority of skin changes associated with ageing are caused by photoageing and reflect cumulative sun exposure. Although the actinic damage plays a major role in skin pigmentation, it is also important to examine the effects of chronological cellular ageing on the pigmentation. The chief cellular components of the skin other than melanocytes are keratinocytes and fibroblasts, and the influences of age-related changes in those cells on skin pigmentation have not been elucidated.

OBJECTIVE

To clarify the effects of cellular ageing of keratinocytes and fibroblasts on age-related skin pigmentation.

METHODS

Using ELISA analysis, we measured the level of melanogenic cytokines secreted by cultured keratinocytes and fibroblasts derived from skin of various chronological ages. We also compared the cytokine secretion by cultured keratinocytes between the second and fifth cultures.

RESULTS

There was no correlation between age and hepatocyte growth factor (HGF), stem cell factor (SCF), and basic fibroblast growth factor (bFGF) secretion by fibroblasts. On the other hand, a significant positive correlation existed between age and interleukin ((IL)-1alpha secretion (R2=0.50, P=0.002), and a relatively weak correlation existed between age and endothelin-1 (ET-1) secretion (R2=0.17, P=0.051, not significant). The IL-1alpha secretion by keratinocytes was significantly increased in the fifth cultures compared with the second cultures (P<0.005).

CONCLUSIONS

These findings suggest that IL-1alpha secretion increases as cells grow older, and the increased secretion of IL-1alpha by aged keratinocytes may stimulate HGF production in dermal fibroblasts paracrinely and ET-1 production in keratinocytes autocrinely, which stimulates melanocyte proliferation and induces an increase of tyrosinase activity in melanocytes. Because IL-1alpha is a primary mediator that responds to inflammation and injury, the transcription of genes involved in skin inflammation may be persistently induced in the aged skin. Thus the increased secretion of IL-1alpha by aged keratinocytes in the aged skin may play a role in the accentuated cutaneous pigmentation and other skin ageing.

摘要

背景

大多数与衰老相关的皮肤变化是由光老化引起的，反映了累积的阳光照射。虽然光化性损伤在皮肤色素沉着中起主要作用，但研究细胞自然老化对色素沉着的影响也很重要。除黑素细胞外，皮肤的主要细胞成分是角质形成细胞和成纤维细胞，这些细胞与年龄相关的变化对皮肤色素沉着的影响尚未阐明。

目的

阐明角质形成细胞和成纤维细胞的细胞老化对与年龄相关的皮肤色素沉着的影响。

方法

使用酶联免疫吸附测定（ELISA）分析，我们测量了来自不同年龄皮肤的培养角质形成细胞和成纤维细胞分泌的黑素生成细胞因子水平。我们还比较了第二代和第五代培养的角质形成细胞的细胞因子分泌情况。

结果

成纤维细胞分泌的肝细胞生长因子（HGF）、干细胞因子（SCF）和碱性成纤维细胞生长因子（bFGF）与年龄之间无相关性。另一方面，年龄与白细胞介素（IL）-1α分泌之间存在显著正相关（R2 = 0.50，P = 0.002），年龄与内皮素-1（ET-1）分泌之间存在相对较弱的相关性（R2 = 0.17，P = 0.051，不显著）。与第二代培养相比，第五代培养的角质形成细胞分泌的IL-1α显著增加（P < 0.005）。

结论

这些发现表明，随着细胞老化，IL-1α分泌增加，老化角质形成细胞分泌增加的IL-1α可能通过旁分泌刺激真皮成纤维细胞产生HGF，并通过自分泌刺激角质形成细胞产生ET-1，从而刺激黑素细胞增殖并诱导黑素细胞中酪氨酸酶活性增加。由于IL-1α是对炎症和损伤作出反应的主要介质，衰老皮肤中参与皮肤炎症的基因转录可能会持续被诱导。因此，老化皮肤中老化角质形成细胞分泌增加的IL-1α可能在皮肤色素沉着加重和其他皮肤老化中起作用。