How Does Chronic Cigarette Smoke Exposure Affect Human Skin? A Global Proteomics Study in Primary Human Keratinocytes

Abstract

Cigarette smoking has been associated with multiple negative effects on human skin. Long-term physiological effects of cigarette smoke are through chronic and not acute exposure. Molecular alterations due to chronic exposure to cigarette smoke remain unclear. Primary human skin keratinocytes chronically exposed to cigarette smoke condensate (CSC) showed a decreased wound-healing capacity with an increased expression of NRF2 and MMP9. Using quantitative proteomics, we identified 4728 proteins, of which 105 proteins were overexpressed (≥2-fold) and 41 proteins were downregulated (≤2-fold) in primary skin keratinocytes chronically exposed to CSC. We observed an alteration in the expression of several proteins involved in maintenance of epithelial barrier integrity, including keratin 80 (5.3 fold, p value 2.5 × 10), cystatin A (3.6-fold, p value 3.2 × 10), and periplakin (2.4-fold, p value 1.2 × 10). Increased expression of proteins associated with skin hydration, including caspase 14 (2.2-fold, p value 4.7 × 10) and filaggrin (3.6-fold, p value 5.4 × 10), was also observed. In addition, we report differential expression of several proteins, including adipogenesis regulatory factor (2.5-fold, p value 1.3 × 10) and histone H1.0 (2.5-fold, p value 6.3 × 10) that have not been reported earlier. Bioinformatics analyses demonstrated that proteins differentially expressed in response to CSC are largely related to oxidative stress, maintenance of skin integrity, and anti-inflammatory responses. Importantly, treatment with vitamin E, a widely used antioxidant, could partially rescue adverse effects of CSC exposure in primary skin keratinocytes. The utility of antioxidant-based new dermatological formulations in delaying or preventing skin aging and oxidative damages caused by chronic cigarette smoke exposure warrants further clinical investigations and multi-omics research.

Nicotinamide (aka Niacinamide) Mitigates SASP-Related Inflammation Induced by Environmental Stressors in Human Epidermal Keratinocytes

“…Nam treatment significantly inhibited the increase of cytokines and prostaglandins synthesized after stress and significantly restored the reduced levels of Lamin B1 (a biomarker known to be lost during senescence) induced by UVB exposure. Relative to cigarette smoke, it has been reported that exposure to keratinocytes can elicit a strong oxidative stress response based on proteomics [41]. We did not detect as strong of a cytokine induction but did see a significant effect of Nam at inhibiting the induced levels of the prostaglandin PGE2.…”

Crocin, a natural molecule with potentially beneficial effects against skin ageing

“…In addition to oxidative stress, the increase in air pollution over the years has been suspected to also play a role in human skin ageing process [8][9][10][11][12][13][14]. A clinical study performed in a polluted environment revealed significant skin differences in superficial biochemical parameters measured on the face of volunteers such as a decrease in squalene, a lipid specific to human sebum which is highly sensitive to oxidation with regard to its six double bonds [15,16].…”

Niacinamide mitigates SASP‐related inflammation induced by environmental stressors in human epidermal keratinocytes and skin

“…Nam treatment significantly inhibited the increase of cytokines and prostaglandins synthesized after stress and significantly restored levels of Lamin B1 (a biomarker known to be lost during senescence) that were reduced by UVB exposure. Relative to cigarette smoke, it has been reported that exposure to keratinocytes can elicit a strong oxidative stress response based on proteomics [36]. We measured an elevated response in PGE 2 production and Nam treatment inhibited these induced levels and also partially reversed the most significant gene expression patterns that were related to apoptosis, DNA repair and cell cycle regulation.…”