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-1beta, 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.
Low molecular weight hyaluronic acid increases the self-defense of skin epithelium by induction of beta-defensin 2 via TLR2 and TLR4 / S. Gariboldi, M. Palazzo, L. Zanobbio, S. Selleri, M. Sommariva, L. Sfondrini, S. Cavicchini, A. Balsari, C. Rumio. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 181:3(2008 Aug), pp. 2103-2110.
|Titolo:||Low molecular weight hyaluronic acid increases the self-defense of skin epithelium by induction of beta-defensin 2 via TLR2 and TLR4|
GARIBOLDI, SILVIA (Primo)
PALAZZO, MARCO (Secondo)
BALSARI, ANDREA (Penultimo)
RUMIO, CRISTIANO (Ultimo)
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
Settore BIO/16 - Anatomia Umana
Settore BIO/17 - Istologia
|Data di pubblicazione:||ago-2008|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.4049/jimmunol.181.3.2103|
|Appare nelle tipologie:||01 - Articolo su periodico|