Contact sensitizers induce skin inflammation via ROS production and hyaluronic acid degradation.

Abstract

BACKGROUND:

Allergic contact dermatitis (ACD) represents a severe health problem with increasing worldwide prevalence. It is a T cell-mediated skin disease induced by protein-reactive organic and inorganic chemicals. A key feature of contact allergens is their ability to trigger an innate immune response that leads to skin inflammation. Previous evidence from the mouse contact hypersensitivity (CHS) model suggests a role for endogenous activators of innate immune signaling. Here, we analyzed the role of contact sensitizer induced ROS production and concomitant changes in hyaluronic acid metabolism on CHS responses.

METHODOLOGY/PRINCIPAL FINDINGS:

We analyzed in vitro and in vivo ROS production using fluorescent ROS detection reagents. HA fragmentation was determined by gel electrophoresis. The influence of blocking ROS production and HA degradation by antioxidants, hyaluronidase-inhibitor or p38 MAPK inhibitor was analyzed in the murine CHS model. Here, we demonstrate that organic contact sensitizers induce production of reactive oxygen species (ROS) and a concomitant breakdown of the extracellular matrix (ECM) component hyaluronic acid (HA) to pro-inflammatory low molecular weight fragments in the skin. Importantly, inhibition of either ROS-mediated or enzymatic HA breakdown prevents sensitization as well as elicitation of CHS.

CONCLUSIONS/SIGNIFICANCE:

These data identify an indirect mechanism of contact sensitizer induced innate inflammatory signaling involving the breakdown of the ECM and generation of endogenous danger signals. Our findings suggest a beneficial role for anti-oxidants and hyaluronidase inhibitors in prevention and treatment of ACD.

• Authors: Philipp R Esser, Ute Wölfle, Christoph Dürr, Friederike D von Loewenich, Christoph M Schempp, Marina A Freudenberg, Thilo Jakob, Stefan F Martin
• Journal: PloS one (PLoS One) Vol. 7 Issue 7 Pg. e41340 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22848468 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Enzyme Inhibitors
• Reactive Oxygen Species
• Hyaluronic Acid
• Hyaluronoglucosaminidase

Topics

• Animals
• Antioxidants (therapeutic use)
• Dermatitis, Allergic Contact (drug therapy, genetics, immunology, pathology)
• Enzyme Inhibitors (therapeutic use)
• Extracellular Matrix (genetics, immunology)
• Hyaluronic Acid (genetics, immunology)
• Hyaluronoglucosaminidase (antagonists & inhibitors, immunology)
• Immunity, Innate
• Mice
• Mice, Mutant Strains
• Reactive Oxygen Species (immunology)
• Skin (immunology, pathology)
• T-Lymphocytes (immunology, pathology)