Mechanisms of “cocktail effects” in skin sensitization – investigation of (danger) signal integration and the role of autophagy in a dendritic cell model
(2019) KIMM01 20191Department of Immunotechnology
Educational programmes, LTH
- Abstract
- Exposure to skin sensitizers on a daily basis has been leading to a high prevalence of allergic contact dermatitis (ACD) among the general population. Single substances have been thoroughly studied for their skin sensitizing potential, yet little is known about the cellular mechanisms of so-called “cocktail effects” of mixtures. It has been suggested that induction of oxidative stress, and more recently, alterations in the autophagic flux, an essential cellular homeostatic mechanism, might play an important role in skin sensitization. These processes might thus also be involved in the appearance of cocktail effects.
The surfactants sodium dodecyl sulfate (SDS) and polyethoxylated tallowamine (POEA) were used in binary SDS/sensitizer and... (More) - Exposure to skin sensitizers on a daily basis has been leading to a high prevalence of allergic contact dermatitis (ACD) among the general population. Single substances have been thoroughly studied for their skin sensitizing potential, yet little is known about the cellular mechanisms of so-called “cocktail effects” of mixtures. It has been suggested that induction of oxidative stress, and more recently, alterations in the autophagic flux, an essential cellular homeostatic mechanism, might play an important role in skin sensitization. These processes might thus also be involved in the appearance of cocktail effects.
The surfactants sodium dodecyl sulfate (SDS) and polyethoxylated tallowamine (POEA) were used in binary SDS/sensitizer and POEA/glyphosate mixtures, respectively, to examine potential cocktail effects of those mixtures in vitro using MUTZ-3-derived cells as a well-established DC model. Cellular responses to single compounds were compared to those to mixtures, investigating the relative change in surface marker expression of CD86, HLA-DR and CD40, indicating DC maturation, intracellular ROS formation and the autophagic flux using flow cytometry.
Cocktail effects could be observed in SDS/sensitizer mixtures, which was compliant with other in vitro and in vivo studies. ROS formation and autophagy induction are most likely involved not just in skin sensitization in general, but also in the appearance of surfactant-induced cocktail effects. (Less) - Popular Abstract
- Constant exposure to skin sensitizing chemical found in food, cosmetic products, jewellery or rubber gloves, just to name a few, can lead to the outbreak of allergic contact dermatitis. This allergic skin condition has a prevalence of almost 20 % among the general European population and develops in a process called skin sensitization. Usually, single compounds are risk assessed before being used in a product. However, mixtures can have a different ability to elicit an immune response compared to their individual ingredients, and little is known about the cellular mechanisms of so-called “cocktail effects” of mixtures.
It is assumed that the formation of reactive oxygen species (ROS) and therefore cellular oxidative stress are important... (More) - Constant exposure to skin sensitizing chemical found in food, cosmetic products, jewellery or rubber gloves, just to name a few, can lead to the outbreak of allergic contact dermatitis. This allergic skin condition has a prevalence of almost 20 % among the general European population and develops in a process called skin sensitization. Usually, single compounds are risk assessed before being used in a product. However, mixtures can have a different ability to elicit an immune response compared to their individual ingredients, and little is known about the cellular mechanisms of so-called “cocktail effects” of mixtures.
It is assumed that the formation of reactive oxygen species (ROS) and therefore cellular oxidative stress are important mechanisms in the skin sensitization process. More recently it was also suggested that alterations in the autophagic flux might play an important role in skin sensitization. Autophagy is an intracellular recycling process, which protects the cell by digesting damaged cytosolic compounds and which provides macromolecules needed growth and maintaining the cellular homeostasis. Oxidative stress responses and the stress-sensitive process autophagy as an essential cellular mechanism might not just be involved in skin sensitization but may also explain the appearance of cocktail effects.
In this thesis, surfactant induced cocktail effects were examined using an in vitro dendritic cell (DC) model. For that purpose, the irritant sodium dodecyl sulfate (SDS) and the former glyphosate-based herbicide ingredient polyethoxylated tallowamine (POEA) were tested in binary SDS/sensitizer or POEA/glyphosate mixtures. SDS was chosen due to previously reported SDS-induced cocktail effect in SDS/sensitizer mixtures, while a POEA/glyphosate mixture was chosen due to controversies regarding the adverse health impact of glyphosate-based herbicides. A well-established DC model based on MUTZ-3-derived cells was used. When analyzing the impact of single compounds and mixtures on the maturation status of the DC-like cells, their ROS-based oxidative stress response and changes in the autophagic flux upon exposure, cocktail effects could be observed in SDS/sensitizer mixtures. This observation was compliant with other in vitro and in vivo studies. ROS formation and autophagy induction are most likely involved not just in skin sensitization in general, but also in the appearance of surfactant-induced cocktail effects, but further studies are needed to better understand the underlying mechanisms. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/8992646
- author
- Werner, Felix LU
- supervisor
- organization
- course
- KIMM01 20191
- year
- 2019
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 8992646
- date added to LUP
- 2019-08-21 13:32:55
- date last changed
- 2019-08-21 13:32:55
@misc{8992646,
abstract = {{Exposure to skin sensitizers on a daily basis has been leading to a high prevalence of allergic contact dermatitis (ACD) among the general population. Single substances have been thoroughly studied for their skin sensitizing potential, yet little is known about the cellular mechanisms of so-called “cocktail effects” of mixtures. It has been suggested that induction of oxidative stress, and more recently, alterations in the autophagic flux, an essential cellular homeostatic mechanism, might play an important role in skin sensitization. These processes might thus also be involved in the appearance of cocktail effects.
The surfactants sodium dodecyl sulfate (SDS) and polyethoxylated tallowamine (POEA) were used in binary SDS/sensitizer and POEA/glyphosate mixtures, respectively, to examine potential cocktail effects of those mixtures in vitro using MUTZ-3-derived cells as a well-established DC model. Cellular responses to single compounds were compared to those to mixtures, investigating the relative change in surface marker expression of CD86, HLA-DR and CD40, indicating DC maturation, intracellular ROS formation and the autophagic flux using flow cytometry.
Cocktail effects could be observed in SDS/sensitizer mixtures, which was compliant with other in vitro and in vivo studies. ROS formation and autophagy induction are most likely involved not just in skin sensitization in general, but also in the appearance of surfactant-induced cocktail effects.}},
author = {{Werner, Felix}},
language = {{eng}},
note = {{Student Paper}},
title = {{Mechanisms of “cocktail effects” in skin sensitization – investigation of (danger) signal integration and the role of autophagy in a dendritic cell model}},
year = {{2019}},
}