Particulate matter increases Cutibacterium acnes-induced inflammation in human epidermal keratinocytes via the TLR4/NF-κB pathway.

Recent studies have demonstrated that particulate matter (PM) can induce oxidative stress and inflammatory responses that are related to the development or exacerbation of several inflammatory dermatoses. However, the effect of PM on acne vulgaris has yet to be determined. In this study, we induced acne-like inflammation in HEKn cells with several concentrations of Cutibacterium acnes (C. acnes) and Staphylococcus aureus peptidoglycan (PGN) to investigate whether PM exposure exacerbates acne-like inflammation and elucidate the underlying mechanisms. To confirm whether PM increases the messenger ribonucleic acid (mRNA) and protein levels of proinflammatory cytokines (IL-1α, IL-1ß, IL-6, IL-8, and TNF-α) and cyclooxygenase (COX)-2 expression in C. acnes- or PGN-treated HEKn cells, we used quantitative real-time polymerase chain reactions, enzyme-linked immunosorbent assays, and western blot assays. The results demonstrated that C. acnes, PGN, and PM induced the expression of proinflammatory cytokines in a time- and dose-dependent manner at the mRNA and protein levels, respectively. Moreover, PM further increased the expression of proinflammatory cytokines, COX2, TLR4, and the phosphorylation of NF-κB in C. acnes- and PGN-treated HEKn cells. In conclusion, our results suggest that PM may exacerbate acne symptoms by increasing the inflammatory response.

Development of In Vitro Co-Culture Model to Mimic the Cell to Cell Communication in Response to Urban PM2.5.

Background: Airborne particulate matter (PM), a widespread air contaminant, is a complex mixture of solids and aerosols composed of particles suspended in the air. PM is associated with inflammatory responses and may worsen inflammatory skin diseases. However, the mechanisms through which PM affects atopic dermatitis (AD) remain unclear. Objective: To establish an in vitro model that more accurately mimics AD using human keratinocyte (HaCaT), dermal fibroblast (HDF), and mast cell (HMC-1) and using this model to investigate the mechanism through which PMs affect AD. Methods: An AD-like in vitro model was established by seeding HaCaT, HDF, and HMC-1 cells with recombinant human interleukin (IL)-1α and polyinosinic:polycytidylic acid. We confirmed the effect of PM on the inflammatory cytokine expression of a triple-cell culture model. SRM 1649b Urban Dust, which is mainly composed of polycyclic aromatic hydrocarbons, was used as the reference PM. The effects of PM on the expression levels of proinflammatory cytokines and skin barrier markers were assessed using quantitative real-time polymerase chain reaction and western blotting. Inflammatory cytokine levels were measured using an enzyme-linked immunosorbent assay. Results: Interactions between various skin cell types were evaluated using a co-culture system. PM treatment increased mRNA and protein levels of the inflammatory cytokines IL-6, IL-1α, tumor necrosis factor-α, IL-4, and IL-1ß and decreased the expression of the skin barrier markers filaggrin and loricrin. Conclusion: Our results suggest that an in vitro triple-cell culture model using HaCaT, HDF, and HMC-1 cells may be reliable for obtaining more physiological, functional, and reproducible data on AD and skin barriers.

In vivo quantitative analysis of advanced glycation end products in atopic dermatitis-Possible culprit for the comorbidities?

Advanced glycation end products (AGEs) interact with the membrane-bound receptor for AGEs (RAGE), consequently amplifying the inflammatory response. Soluble receptor for AGE (sRAGE) and endogenous secretory RAGE (esRAGE) act as decoys for AGE and competitively sequester RAGE ligands, thereby serving a cytoprotective role. Our objective was to investigate AGE expression and their receptors in the serum and skin of patients with atopic dermatitis (AD). In this case-control study, the levels of AGE, sRAGE and esRAGE were measured in the blood samples and corneocytes of 29 adult patients with AD and 12 healthy controls by ELISA. Corneocyte AGE levels increased in the AD group (P = .002). Higher corneocyte AGE levels were observed in the severe AD than in the milder form of AD. No significant difference in serum AGE level was observed in patients with AD and healthy controls. Serum sRAGE markedly decreased in patients with AD (P = .007) and serum esRAGE followed a similar trend. In conclusion, dermal accumulation of AGE in AD may have a role in fuelling skin inflammation. The potential after-effects of reduced neutralizer on systemic risk need further evaluation.