The skin of an organism is affected by various environmental factors and fights against aging stress via mechanical and biochemical responses. Photoaging induced by ultraviolet B (UVB) irradiation is common and is the most vital factor in the senescence phenotype of skin, and so, suppression of UVB stress-induced damage is critical. To lessen the UVB-induced hyperimmune response and hyperpigmentation, we investigated the ameliorative effects of intense pulsed light (IPL) treatment on the photoaged phenotype of skin cells. Normal human epidermal keratinocytes and human epidermal melanocytes were exposed to 20 mJ/cm² of UVB. After UVB irradiation, the cells were treated with green (525–530 nm) and yellow (585–592 nm) IPL at various time points prior to the harvest step. Subsequently, various signs of excessive immune response, including expression of proinflammatory and melanogenic genes and proteins, cellular oxidative stress level, and antioxidative enzyme activity, were examined. We found that IPL treatment reduced excessive cutaneous immune reactions by suppressing UVB-induced proinflammatory cytokine expression. IPL treatment prevented hyperpigmentation, and combined treatment with green and yellow IPL synergistically attenuated both processes. IPL treatment may exert protective effects against UVB injury in skin cells by attenuating inflammatory cytokine and melanogenic gene overexpression, possibly by reducing intracellular oxidative stress. IPL treatment also preserves antioxidative enzyme activity under UVB irradiation. This study suggests that IPL treatment is a useful strategy against photoaging, and provides evidence supporting clinical approaches with non-invasive light therapy.

Particulate matters (PMs) increase oxidative stress and inflammatory response in different tissues. PMs disrupt the formation of primary cilia in various skin cells, including keratinocytes and melanocytes. In this study, we found that 2-isopropylmalic acid (2-IPMA) promoted primary ciliogenesis and restored the PM2.5-induced dysgenesis of primary cilia in dermal fibroblasts. Moreover, 2-IPMA inhibited the generation of excessive reactive oxygen species and the activation of stress kinase in PM2.5-treated dermal fibroblasts. Further, 2-IPMA inhibited the production of pro-inflammatory cytokines, including IL-6 and TNF-α, which were upregulated by PM2.5. However, the inhibition of primary ciliogenesis by IFT88 depletion reversed the downregulated cytokines by 2-IPMA. Moreover, we found that PM2.5 treatment increased the MMP-1 expression in dermal fibroblasts and a human 3-D-skin model. The reduced MMP-1 expression by 2-IPMA was further reversed by IFT88 depletion in PM2.5-treated dermal fibroblasts. These findings suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in dermal fibroblasts.

Primary cilia mediate the interactions between cells and external stresses. Thus, dysregulation of primary cilia is implicated in various ciliopathies, e.g., degeneration of the retina caused by dysregulation of the photoreceptor primary cilium. Particulate matter (PM) can cause epithelium injury and endothelial dysfunction by increasing oxidative stress and inflammatory responses. Previously, we showed that PM disrupts the formation of primary cilia in retinal pigment epithelium (RPE) cells. In the present study, we identified 2-isopropylmalic acid (2-IPMA) as a novel inducer of primary ciliogenesis from a metabolite library screening. Both ciliated cells and primary cilium length were increased in 2-IPMA-treated RPE cells. Notably, 2-IPMA strongly promoted primary ciliogenesis and restored PM2.5-induced dysgenesis of primary cilia in RPE cells. Both excessive reactive oxygen species (ROS) generation and activation of a stress kinase, JNK, by PM2.5 were reduced by 2-IPMA. Moreover, 2-IPMA inhibited proinflammatory cytokine production, i.e., IL-6 and TNF-α, induced by PM2.5 in RPE cells. Taken together, our data suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in RPE cells.

Particulate matter 2.5 (PM_2.5), an atmospheric pollutant with an aerodynamic diameter of <2.5 μm, can cause serious human health problems, including skin damage. Since sebocytes are involved in the regulation of skin homeostasis, it is necessary to study the effects of PM_2.5 on sebocytes. We examined the role of PM_2.5 via the identification of differentially expressed genes, functional enrichment and canonical pathway analysis, upstream regulator analysis, and disease and biological function analysis through mRNA sequencing. Xenobiotic and lipid metabolism, inflammation, oxidative stress, and cell barrier damage-related pathways were enriched; additionally, PM_2.5 altered steroid hormone biosynthesis and retinol metabolism-related pathways. Consequently, PM_2.5 increased lipid synthesis, lipid peroxidation, inflammatory cytokine expression, and oxidative stress and altered the lipid composition and expression of factors that affect cell barriers. Furthermore, PM_2.5 altered the activity of sterol regulatory element binding proteins, mitogen-activated protein kinases, transforming growth factor beta-SMAD, and forkhead box O3-mediated pathways. We also suggest that the alterations in retinol and estrogen metabolism by PM_2.5 are related to the damage. These results were validated using the HairSkin^® model. Thus, our results provide evidence of the harmful effects of PM_2.5 on sebocytes as well as new targets for alleviating the skin damage it causes.

Post-inflammatory hyperpigmentation (PIH) results from inflammatory responses that leave persistent dark spots around pores after acne lesions are resolved. This pigmentation is caused by increased melanogenesis in melanocytes stimulated by acne-causing bacteria, followed by phagocytosis of excess melanin by macrophages that remain in the dermis. Therefore, to eliminate PIH caused by acne, it is essential not only to suppress excessive melanin synthesis by melanocytes but also to promote the degradation of melanin retained within macrophages. In this study, we investigated whether a culture extract of Bacillus velezensis AmoreLumina (AL), containing more than 80% moranoline (1-Deoxynojirimycin), could inhibit acne-induced pigmentation. Moranoline reduces melanin synthesis by inhibiting the glycosylation of tyrosinase, a key melanogenic enzyme, thereby suppressing its activity. The extract suppressed the upregulation of melanogenic enzymes (tyrosinase, TRP1, and TRP2) and melanin production in melanocytes exposed to acne bacteria, while promoting melanin degradation via macrophage lysosomal activity, as assessed by the relative protein expression level of p62 using Western blotting. Furthermore, in an ex vivo human skin model subjected to acne and ultraviolet radiation-induced pigmentation, treatment with the extract (0.2%) significantly reduced pigmentation (relative delta L 2.98, p value < 0.01). These findings suggest that cosmetic or pharmaceutical formulations incorporating AL extract or moranoline may potentially improve PIH caused by acne-related inflammation.