Skin under pressure: tension affects skin's reaction to pollution

In a recent article published in Scientific Reportsresearchers ratified previous findings that ozone (O3) exposure (an air pollutant) alters the antimicrobial peptides (AMPs) expression in the skin with and without tension.

Study: Tension as a key factor in skin responses to pollution. Image Credit: Geinz Angelina/
Study: Tension as a key factor in skin responses to pollution. Image Credit: Geinz Angelina/

Being key effectors in innate immune responses, AMPs, 12–100 amino acid long peptides, kill a broad spectrum of pathogens. A previous study showed that the redox-sensitive upregulation of AMPs upon O3 exposure contributed to the development of inflammatory skin conditions.

Since AMPs aid skin immunity but contribute to multiple inflammatory skin conditions, such as psoriasis and acne vulgaris, to name a few, it is crucial to determine whether AMPs induced by O3 exposure inhibit or promote cutaneous inflammation.


The World Health Organization (WHO) states that ~91% of the cities-based world population inhales polluted air, leading to over four million premature deaths annually. The United States Department of Agriculture (USDA) has categorized air pollutants (based on their physical and chemical properties) into six categories, viz., carbon monoxide (CO), ozone (O3), lead (Pb), nitrogen dioxide (NO2), sulfur dioxide (SO2), and particulate matter (PM), of which O3 is the most dangerous and toxic due to its high reactivity with the skin.

Studies have reported persistently high concentrations of O3 in urban centers, ranging between 0.5 and 0.8 parts per million (ppm) during severe pollution. Mostly, cities across the WHO set a threshold of ozone exposure (0.05 ppm), so, clearly, 9/10 people breathe severely polluted air, way above the current recommended guidelines.

Note that ~90% of ozone exists in the stratosphere, where it absorbs ultraviolet (UV) radiation in the sunlight; however, O3 has an anthropogenic origin, too. This ozone remains in the troposphere after originating from photochemical smog, i.e., the chemical reaction between UV rays, nitrogen oxides, and hydrocarbons.

Regarding the mechanism by which O3 induces cutaneous damage, it is noteworthy that it directly interacts with and oxidizes polyunsaturated fatty acids (PUFAs) and lipids in the SC, leading to the generation of aldehydes and reactive oxygen species (ROS), which further promote ozone toxicity to perpetuate the damage in deeper cutaneous layers.

The production of ROS also triggers inflammatory responses, which, in turn, activate harmful pathways, such as pro-inflammatory transcription factors (NFkβ) and intracellular mitogen-activated protein kinases (MAPK). These degrade the connective dermal tissue via metalloproteinases, matrix metallopeptidase 9 (MMP9), and other pro-inflammatory mediators [e.g., interleukin-18 (IL-18), IL-1β].

Pollutants such as PMs, O3, and UV can activate aryl hydrocarbon receptors (AhR), which, in turn, could further promote ROS production and enhance the OxInflammatory tissue responses, a vicious crosstalk loop between inflammation and oxidative stress.

Due to the presence of elastic fibers in the dermis, the skin has a degree of mechanical elasticity that maintains a state of constant tension, which is fundamental for maintaining skin integrity and flexibility. It also helps the skin maintain functions, such as extracellular matrix (ECM) production and response to external stimuli. 

Tensional homeostasis is the balance between the extracellular forces on skin cells [e.g., ECM] and the traction forces generated by the cells and is significant at the organ and cellular levels.

Researchers have developed and used multiple different skin models to study cutaneous responses to pollution, e.g., in vitro two-dimensional (2D) cell lines and 3D cutaneous models, in vivo models using animal/human donors, and ex vivo skin explants, with each having some limitations and some advantages.

So, while 2D cell lines are economical, accessible, and reproducible, they failed to generate the stratum corneum (SC), the outermost skin layer highly affected by O3 exposure. 3D models formed the SC, but not all SC layers. So far, ex vivo human skin explants are the best to examine cutaneous responses as they have all the skin layers, immune cells, and skin appendages, such as sweat glands and hair follicles, that produce AMPs. Unfortunately, even these models lack the physiological tissue tension present in human skin.

About the study

In the present study, researchers used the TenSkin™ model that uses ex vivo human skin explants cultured under physiologically relevant tension to demonstrate the importance of skin tension in interactions between skin and environmental stressors, such as O3

Additionally, they explored whether tensional homeostasis in the skin anticipated, delayed, or prolonged the OxInflammatory cutaneous response to O3 compared to non-tension skin exposed to O3.

Based on the findings of a previous in vitro study, they hypothesized that O3 exposure triggers upregulation of cutaneous AMPs in tissues with and without tension, most likely due to oxidative stress.

Three healthy subjects donated ex vivo human skin explants, from which the team cultured 50% under physiologically relevant tension (tension skin, Ten), while the other 50% without tension (NT).

They exposed these skin explants to O3 for four hours at a dose of 0.4 ppm. Next, the team collected skin samples at zero, three, six, and 24 hours, T0, T3, T6 and T24. Then, they performed protein, RNA, and immunohistochemical analyses of these samples. Finally, the researchers used quantitative real-time polymerase chain reaction (RT-qPCR) to quantify the gene expression.


The current study could not determine why ozone exposure increases AMPs; however, it confirmed that tension modulated the expression levels of AMP genes and proteins, such as cathelicidin antimicrobial peptide (CAMP)/LL-37, human beta-defensins (hBD)2/3.

The authors also noted varying responses between tension and non-tension cultured skin while evaluating OxInflammatory markers, including cyclooxygenase-2 (COX2), AhR, MMP9, and 4-hydroxy-nonenal (4HNE). 

The study findings confirmed the correlation between AMPs and oxidative stress markers upon O3 exposure in tissues cultured with and without tensional homeostasis. Furthermore, the researchers detected an anticipated increase (T0, T3) of some protein levels, including hBD3 and cyclooxygenase-2 (COX2), in non-tension skin compared to tension skin upon O3 exposure.


The current study ratified previous findings that pollution induces the cutaneous expression of AMPs via redox signaling. More importantly, this study validated the knowledge that the use of skin biopsies is ideal when it comes to examining skin responses. Thus, the Ten Bio model could prove beneficial to studying pollutants that interact with the SC, conducting physiological tests, such as drug delivery tests, and evaluating aspects closely resembling biological responses.

Future studies should focus on gathering data concerning the molecular mechanisms governing the cutaneous tension responses to environmental stressors-induced AMP expression and oxidative stress for insights into real-life scenarios.

Journal reference:
Neha Mathur

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.


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