Document Detail

Low molecular weight hyaluronic acid increases the self-defense of skin epithelium by induction of beta-defensin 2 via TLR2 and TLR4.
MedLine Citation:
PMID:  18641349     Owner:  NLM     Status:  MEDLINE    
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.
Silvia Gariboldi; Marco Palazzo; Laura Zanobbio; Silvia Selleri; Michele Sommariva; Lucia Sfondrini; Stefano Cavicchini; Andrea Balsari; Cristiano Rumio
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  181     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-21     Completed Date:  2008-08-19     Revised Date:  2010-09-17    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2103-10     Citation Subset:  AIM; IM    
Mucosal Immunity Laboratory, Department of Human Morphology, Università degli Studi di Milano, Milan, Italy.
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MeSH Terms
Anti-Bacterial Agents / pharmacology
Cell Extracts / pharmacology
Cell Line
Cytokines / biosynthesis
Epithelium / drug effects,  immunology,  metabolism,  secretion
Escherichia coli / drug effects
Gene Expression Regulation / drug effects
Hyaluronic Acid / pharmacology*
Keratinocytes / drug effects,  immunology,  metabolism,  secretion
Lipopolysaccharides / pharmacology
Mice, Inbred C57BL
Mice, Knockout
Molecular Weight
Peptidoglycan / pharmacology
Protein Kinase C / metabolism
Proto-Oncogene Proteins c-fos / metabolism
Signal Transduction
Skin / drug effects*,  immunology,  metabolism*,  secretion
Toll-Like Receptor 2 / agonists,  metabolism*
Toll-Like Receptor 4 / deficiency,  genetics,  metabolism*
beta-Defensins / genetics,  metabolism*,  secretion
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Cell Extracts; 0/Cytokines; 0/DEFB4A protein, human; 0/Defb2 protein, mouse; 0/Lipopolysaccharides; 0/Peptidoglycan; 0/Proto-Oncogene Proteins c-fos; 0/Toll-Like Receptor 2; 0/Toll-Like Receptor 4; 0/beta-Defensins; 9004-61-9/Hyaluronic Acid; EC Kinase C

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