Paracrine cytokine interaction between UVB-exposed epidermal keratinocytes and dermal fibroblasts in stimulating expression of skin fibroblast-derived elastase

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• 作者：Hiroaki Nakajima ; Ryosuke Yoshioka ; Yoshiyuki Ezaki ; Tomoyashu Nagai ; Genji Imokawa ; ^{imokawag@dream.ocn.ne.jp}
• 关键词：GM-CSF ; granulocyte macrophage colony stimulatory factor ; IL-1伪 ; Interleukin-1伪 ; NEP ; neutral endopeptidase ; SFE ; skin fibroblast-derived elastase ; STANA ; N-succinyl-tri-alanyl-p-nitroaniline ; UVB ; ultraviolet B ; MMP-1 ; matrix-meltalloproteinase-1
• 刊名：Cytokine
• 出版年：2012
• 期刊代码：97_10434666
• 类别：imm
• 出版时间：July, 2012
• 卷：59
• 期：1
• 页码：166-175
• 文件大小：2226 K

摘要

Background

We recently reported that over-expression of skin fibroblast-derived elastase (SFE) plays a pivotal role in the mechanism of UVB-induced skin wrinkling. Since UVB penetrates only modestly to the dermis, we hypothesized that factors secreted by UVB-exposed keratinocytes in the epidermis trigger fibroblasts in the dermis to increase their expression of SFE which then degrades the elastic fibers.

Objective

In this study, we characterized the paracrine interaction between human keratinocytes (HK) and human fibroblasts (HF) which leads to increased expression of SFE.

Methods and results

Medium conditioned by UVB-exposed HK contained increased levels of IL-1伪, GM-CSF, IL-6, TNF伪 and IL-8. While HF cultured with those conditioned medium slightly down-regulated the gene expression of collagen and elastin, they significantly increased their expression of SFE at the transcriptional, translational and enzymatic levels. Neutralizing antibodies to IL-1伪 or GM-CSF significantly abolished the increased expression of SFE at the translational and/or enzymatic levels in HF cultured with those conditioned medium, while neutralizing antibodies to IL-6, IL-8 or TNF伪 had no such effect. The addition of IL-1伪 or GM-CSF, but not TNF伪, IL-6 or IL-8, at concentrations ranging from 1 to 10 nm, significantly stimulated the enzymatic levels of SFE in HF.

Conclusions

The sum of these findings suggests that IL-1伪 and GM-CSF are intrinsic cytokines secreted by UVB-exposed HK that stimulate expression of SFE by HF, leading to UVB-induced wrinkle formation.