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

Objective: To evaluate whether niacinamide (Nam) can mitigate production of inflammatory and senescence-related biomarkers induced by environmental stressors.

Methods: Human epidermal keratinocytes were exposed to UVB, urban dust, diesel exhaust, and cigarette smoke extract and treated with Nam or vehicle control. Full thickness 3-D skin organotypic models were exposed to a combination of UVB and PM_2.5 and treated with Nam or vehicle control. Quantitation of the SASP-related inflammatory mediators PGE₂ , IL-6, and IL-8 was performed on cultured media. UVB-exposed keratinocytes treated with and without Nam were immunostained for the senescence biomarker Lamin B1 (LmnB1). Transcriptomics profiling of cigarette smoke extract effects on keratinocytes was performed. A placebo controlled double blinded clinical was conducted on 40 female panelists that were pretreated on back sites for two weeks with 5% Nam or vehicle and then exposed to 1.5 minimal erythemal dose (MED) solar simulated radiation (SSR). Treated sites were compared to non-treated exposed sites for erythema and the skin surface IL-1αRA/IL-1α inflammatory biomarkers.

Results: UVB induced synthesis of PGE₂ , IL-8 and IL-6 and reduced LmnB1 levels in keratinocytes. Urban dust and diesel exhaust only stimulated synthesis of IL-8 whereas cigarette smoke extract only stimulated levels of PGE₂ . In all exposures, treatment with Nam significantly mitigated synthesis of the inflammatory mediators and restored levels of UVB-reduced LmnB1. In the 3D skin equivalent model, Nam reduced IL-8 levels stimulated by a combination of topical PM_2.5 and UV exposure. In a UV-challenge clinical, pretreatment with 5% Nam reduced erythema and skin surface IL-1αRA/IL-1α inflammatory biomarkers that were induced by SSR.

Conclusion: Since it is known that Nam has anti-inflammatory properties, we tested whether Nam can inhibit environmental stress induced inflammation and senescence-associated secretory phenotype (SASP) biomarkers. We show Nam can reduce PGE₂ , IL-6, and IL-8 levels induced by environmental stressors. Additionally, in vivo pretreatment with Nam can reduce UV-induced erythema and skin surface inflammatory biomarkers. These findings add to the body of evidence that Nam can mitigate the skin's inflammatory response elicited by environmental stressors. This supports Nam can potentially inhibit senescence and premature aging and thereby maintain skin's functionality and appearance.

Keywords: cell culture; claim substantiation; environmental stressors; inflammation; niacinamide; skin physiology/structure.