Particulate matter induces pro‐inflammatory cytokines via phosphorylation of p38 MAPK possibly leading to dermal inflammaging

Abstract

Particulate matter (PM) is known to have harmful effects on human health. Epidemiological studies have suggested that PM exposure is related to skin diseases and extrinsic skin ageing. However, the mechanisms by which PM affects skin are unclear. The aim of this study was to investigate the mechanism of action of PMs on epidermal inflammation and skin ageing using a co‐culture of human keratinocytes (HaCaT) and fibroblasts (HDF). SRM 1648a (pmA) and 1649b (pmB), which mainly comprise heavy metals and polycyclic aromatic hydrocarbons, respectively, were used as reference PMs. Cytotoxic effects, activation of AhR, phosphorylation of p38 kinase and ROS generation were examined in PM‐treated HaCaT cells. The phosphorylation of p38 MAPK induced by PMs was shown to be critically important for the increases in IL‐1α and IL‐1β expression. Moreover, the mRNA and protein expression levels of MMP1 and COX2 were markedly increased in HDF cells co‐cultured with PM‐treated HaCaT cells. In conclusion, PMs induce the expression of pro‐inflammatory cytokines in keratinocytes via the p38 MAPK pathway, and these interleukins increase the expression of MMP1 and COX2 in HDF cells. These results suggest that PMs trigger skin ageing via p38 MAPK activation and interleukin secretion in epidermal keratinocytes.

Evidence for the critical role of the PI3K signaling pathway in particulate matter-induced dysregulation of the inflammatory mediators COX-2/PGE2 and the associated epithelial barrier protein Filaggrin in the bronchial epithelium

“…It has been previously reported that oxidative stress is primordial to explain the toxic effects generated by PM exposure. Important studies have demonstrated that PM exposure leads to ROS-dependent activation of signaling pathways mediating the pathological processes, including the MAPK signaling pathway (Dou et al 2018;Kim et al 2019;Liu et al 2019;Tsai et al 2017). Previous research reported ERK, JNK, and PI3K/AKT activation in the lung following lipopolysaccharide stimulation (Chen et al 2011;Shi et al 2018).…”

Impact of airborne particulate matter on skin: a systematic review from epidemiology to in vitro studies

“…Upon binding to its ligand, the AhR translocates from the cytoplasm to the nucleus, where it forms a dimer with the AhR nuclear translocator (ARNT) [202]. PM induces the nuclear translocation of AhR in vitro [119,124,171,172,178]. The AhR/ARNT complex binds to conserved promoter regions containing the xenobiotic response element (XRE), promoting the transcription of several groups of target genes, such as from the phase I metabolism (e.g., cytochrome P450 family 1 subfamily A member 1, CYP1A1, CYP1A2, and CYP1B1), the phase II metabolism (e.g., UDP glucuronosyltransferase family 1 member A complex locus, UGT1A and glutathione S-transferase A1, GSTA1) and a gene for the arylhydrocarbon receptor repressor (AhRR) [203].…”

“…CYP enzymes can metabolize PAHs, and the formed metabolites can induce cell damage either by the formation of DNA, protein adducts, or the generation of ROS [195,[204][205][206][207][208]. Indeed, PM upregulates the CYP enzyme mRNA and protein expression in vitro and in vivo [119,128,129,134,135,139,141,167,171,172,178,187]. Other ROS producing enzymes are the members of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) family [209].…”

“…This activation of downstream signaling pathways results in the activation of MAPK members, such as extracellular-signal-regulated kinase (ERK), c-Jun-NH2-terminal kinase (JNK), p38, but also the transcription factor adaptor protein 1 (AP-1) [252]. Exposure of fibroblasts and keratinocytes to PM was shown to induce the activation of the MAPK pathway by the phosphorylation of ERK, JNK, and p38 [130,136,143,168,172,178,179,181,184].…”

Role of Mitochondria in the Redox Signaling Network and Its Outcomes in High Impact Inflammatory Syndromes

“…Once in the nucleus, those transcription factor promote the transcription of a variety of proinflammatory cytokines, including TNF-α, IL-1a, IL-6, and IL-8. IL-1α and IL-1β in keratinocytes (144). In addition, PM-induce ROS production through the NOX4 activation stimulates NF-κB translocation and increased transcript levels of cytokines (145).…”