Low molecular weight hyaluronic acid increases the self-defense of skin epithelium by induction of β-defensin 2 via TLR2 and TLR4
Low molecular weight hyaluronic acid increases the self-defense of skin epithelium by induction of β-defensin 2 via TLR2 and TLR4
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DOI：
10.4049/jimmunol.181.3.2103
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发表时间：
2008-08-01
影响因子：
4.4
通讯作者：
Rumio, Cristiano
中科院分区：
文献类型：
--
作者：
Gariboldi, Silvia;Palazzo, Marco;Rumio, Cristiano
在炎症或组织损伤部位，细胞外基质中普遍存在的透明质酸 (HA) 被分解成低分子量的物质。据报道，HA (LMW-HA) 片段可激活免疫活性细胞。我们发现 LMW-HA 诱导角质形成细胞激活，角质形成细胞通过产生 β-防御素 2 做出反应。这种产生由 TLR2 和 TLR4 激活介导，并涉及 c-Fos 介导的蛋白激酶 C 依赖性信号通路。 LMW-HA 诱导的角质形成细胞活化似乎不伴随炎症反应，因为没有观察到 IL-8、TNF-α、IL-1β 或 IL-6 的产生。用 LMW-HA 对小鼠皮肤进行离体和体内处理，结果显示小鼠 β-防御素 2 在表皮区室的所有层中释放。因此，细胞外基质成分的分解（例如在受伤后）会刺激角质形成细胞释放β-防御素2，从而在皮肤组织特别容易受到感染时保护皮肤组织。此外，我们的观察可能对于开发含有LMW-HA的可能的局部产品的新视角很重要，以改善角质形成细胞释放β-防御素，从而改善皮肤的自我防御，保护皮肤组织免受微生物感染。
In sites of inflammation or tissue injury, hyaluronic acid (HA), ubiquitous in the extracellular matrix, is broken down into low m.w. HA (LMW-HA) fragments that have been reported to activate immunocompetent cells. We found that LMW-HA induces activation of keratinocytes, which respond by producing beta-defensin 2. This production is mediated by TLR2 and TLR4 activation and involves a c-Fos-mediated, protein kinase C-dependent signaling pathway. LMW-HA-induced activation of keratinocytes seems not to be accompanied by an inflammatory response, because no production of IL-8, TNF-alpha, IL-1 beta, or IL-6 was observed. Ex vivo and in vivo treatments of murine skin with LMW-HA showed a release of mouse beta-defensin 2 in all layers of the epidermal compartment. Therefore, the breakdown of extracellular matrix components, for example after injury, stimulates keratinocytes to release beta-defensin 2, which protects cutaneous tissue at a time when it is particularly vulnerable to infection. In addition, our observation might be important to open new perspectives in the development of possible topical products containing LMW-HA to improve the release of beta-defensins by keratinocytes, thus ameliorating the self-defense of the skin for the protection of cutaneous tissue from infection by microorganisms.