Particulate matter induces inflammatory cytokine production via activation of NFκB by TLR5-NOX4-ROS signaling in human skin keratinocyte and mouse skin

Abstract

Particulate matter (PM) increases levels of pro-inflammatory cytokines, but its effects on the skin remain largely unknown. We investigated the signal transduction pathway and epigenetic regulatory mechanisms underlying cellular inflammation induced by PM with a diameter of ≤ 2.5 (PM2.5) in vitro and in vivo. PM2.5-treated skin keratinocytes produced various inflammatory cytokines, including IL-6. The binding of PM2.5 to TLR5 initiated intracellular signaling through MyD88, and led to the translocation of NFκB to the nucleus, where it bound the NFκB site within IL-6 promoter. Furthermore, PM2.5 induced a direct interaction between TLR5 and NOX4, and in turn induced the production of ROS and activated NFκB-IL-6 downstream, which was prevented by siRNA-mediated knockdown of NOX4 or antioxidant treatment. Furthermore, expression of TLR5, MyD88, NOX4, phospho-NFκB, and IL-6 was increased in skin tissue of PM2.5-treated flaky tail mice. PM2.5-induced increased transcription of IL-6 was regulated via DNA methylation and histone methylation by epigenetic modification; the binding of DNA demethylase and histone methyltransferase to the IL-6 promoter regions resulted in increased IL-6 mRNA expression. Our findings provide deep insight into the pathogenesis of PM2.5 exposure and can be used as a therapeutic strategy to treat inflammatory skin diseases caused by PM2.5 exposure.

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

“…Similar to what is known with UV exposure, pollution (particulate matter) has been reported to trigger inflammation in keratinocytes [36,37]. While an inflammatory response can resolve poststress, it has been suggested that this resolution becomes less efficient with aging and leads to a persistent sub-chronic inflammatory state.…”

Protective Effect of Diphlorethohydroxycarmalol Isolated from Ishige okamurae Against Particulate Matter-Induced Skin Damage by Regulation of NF-κB, AP-1, and MAPKs Signaling Pathways In Vitro in Human Dermal Fibroblasts

“…Exposure to PM causes epithelium damage, and endothelial dysfunction has been reported previously [8,9,38]. PM induce skin damages or diseases mainly through stimulating inflammatory response and oxidative stress [5,39]. Ryu et al investigated that PM induced epidermic inflammatory response in human keratinocytes [39].…”

“…PM induce skin damages or diseases mainly through stimulating inflammatory response and oxidative stress [5,39]. Ryu et al investigated that PM induced epidermic inflammatory response in human keratinocytes [39]. The results indicated that PM significantly stimulated the expression of pro-inflammatory cytokines through activating NF-κB pathway [39].…”

“…Ryu et al investigated that PM induced epidermic inflammatory response in human keratinocytes [39]. The results indicated that PM significantly stimulated the expression of pro-inflammatory cytokines through activating NF-κB pathway [39]. Piao et al evaluated the effect of PM on human keratinocytes, and the results indicated that PM significantly induced oxidative stress by production of ROS, which causes lipid peroxidation, DNA damage, and protein carbonylation [9].…”

The Antitumor Efficacy of β-Elemene by Changing Tumor Inflammatory Environment and Tumor Microenvironment

“…When the body is infected or repairs wounds, it permanently activates and chemotactically accumulates a large number of white blood cells (such as macrophages, neutrophils, lymphocytes, and dendritic cells) at the site of injury by releasing cytokines/chemokines (such as interleukin-6/10 (IL-6/10) [38,39] and tumor necrosis factor-α (TNF-α)) [40], growth factors (transforming growth factor-β (TGF-β)) [41], matrix metalloproteinases (MMPs) [42], vascular endothelial growth factor (VEGF) [43], reactive oxygen species (ROS) metabolites, and other substances [44]. These inflammatory cytokines not only recruit inflammatory cells to amplify inflammation at the tumor site [45] but also form a new environment [46], leading to the destruction and atrophy of normal tissues [47] and promoting mass production of the tumor matrix and blood vessels [48].…”