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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- Silvia Gariboldi
- *Mucosal Immunity Laboratory, Department of Human Morphology and
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- Marco Palazzo
- *Mucosal Immunity Laboratory, Department of Human Morphology and
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- Laura Zanobbio
- *Mucosal Immunity Laboratory, Department of Human Morphology and
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- Silvia Selleri
- *Mucosal Immunity Laboratory, Department of Human Morphology and
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- Michele Sommariva
- *Mucosal Immunity Laboratory, Department of Human Morphology and
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- Lucia Sfondrini
- †Institute of Pathology, Università degli Studi di Milano, Milan, Italy;
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- Stefano Cavicchini
- ‡Unità Operativa Dermatologia, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy; and
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- Andrea Balsari
- †Institute of Pathology, Università degli Studi di Milano, Milan, Italy;
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- Cristiano Rumio
- *Mucosal Immunity Laboratory, Department of Human Morphology and
説明
<jats:title>Abstract</jats:title> <jats:p>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 β-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-α, IL-1β, or IL-6 was observed. Ex vivo and in vivo treatments of murine skin with LMW-HA showed a release of mouse β-defensin 2 in all layers of the epidermal compartment. Therefore, the breakdown of extracellular matrix components, for example after injury, stimulates keratinocytes to release β-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 β-defensins by keratinocytes, thus ameliorating the self-defense of the skin for the protection of cutaneous tissue from infection by microorganisms.</jats:p>
収録刊行物
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- The Journal of Immunology
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The Journal of Immunology 181 (3), 2103-2110, 2008-08-01
The American Association of Immunologists