Mechanistic understanding of the relationship between oxidative and electrophilic stress in allergic skin sensitisation

Abstract

Allergic skin sensitisation manifests clinically as allergic contact dermatitis (ACD), an inflammatory disease of the skin that affects roughly 20% of the European population. ACD is caused by a delayed immune response to skin proteins modified by small molecule electrophiles, sensitisers.
Oxidative and electrophilic stress are series of complex cellular responses to normal physiological and pathophysiological processes. Accumulation of reactive oxygen species (ROS) causes the generation of reactive electrophiles that can bind proteins, lipids. Cells possess antioxidant mechanisms such as glutathione (GSH) that scavenge, bind, and render ROS and electrophiles inert.
Antioxidant response element gene activation is a key event in allergic skin sensitisation. Additionally, GSH has been shown to bind and eliminate model skin sensitisers including 2,4-dinitrochlorobenzene (DNCB). The mechanisms of the role(s) of oxidative stress in sensitisation are incompletely characterised.
Using proteomics methods with in vitro HaCaT human keratinocytes, this project aims to improve our understanding of the role(s) of oxidative stress in allergic skin sensitisation. Data suggests that ROS induced oxidative stress leads to increased activity of catalase, inhibition of superoxide dismutase, and depletion of GSH following exposure to the sensitiser DNCB. However, protein signalling pathways that could increase generation of ROS and potentially leave keratinocytes vulnerable to increased oxidative and electrophilic damage following DNCB exposure do not appear to be significantly altered by a pre-existing state of ROS induced oxidative stress.

More information

Identifiers

ORCID for Scott David Adams: orcid.org/0000-0001-6775-856X

ORCID for Paul Skipp: orcid.org/0000-0002-2995-2959

ORCID for Max Crispin: orcid.org/0000-0002-1072-2694

Catalogue record

Export record