Heparinoid suppresses Der p‐inducedIL‐1β production by inhibitingERKand p38MAPKpathways in keratinocytes

Abstract

Epidermal keratinocytes initiate skin inflammation by activating immune cells. The skin barrier is disrupted in atopic dermatitis (AD) and epidermal keratinocytes can be exposed to environmental stimuli, such as house dust mite (HDM) allergens. We showed previously that HDM allergens activate the NLRP3 inflammasome of keratinocytes, thereby releasing pro-inflammatory cytokines. Heparinoid is an effective moisturizer for atopic dry skin. However, a recent report showed that heparinoid treatment can improve inflammation of lichen planus. Therefore, we hypothesized that it acts on epidermal keratinocytes not only as a moisturizer, but also as a suppressant of the triggers of skin inflammation. We found that HDM allergen-induced interleukin (IL)-1β release from keratinocytes was inhibited significantly by heparinoid pretreatment without affecting cell viability. However, heparinoid did not affect caspase-1 release, suggesting that heparinoid did not affect HDM allergen-induced inflammasome activation. Heparinoid treatment not only decreased intracellular levels of pro-IL-1β, but also suppressed IL-1β messenger RNA (mRNA) expression in keratinocytes. Among the intracellular signalling pathways, the activation of extracellular signal-regulated kinase and p38 pathways, which are required for IL-1β expression in keratinocytes, was inhibited by heparinoid treatment. The inhibitory effect of heparinoid on IL-1β mRNA expression was also confirmed with living skin equivalents. Our results demonstrated that heparinoid suppresses the initiation of keratinocyte-mediated skin inflammation.

High-mobility group box 1 (HMGB1) in COVID-19: extrapolation of dangerous liaisons

“…Therefore, heparin mitigates inflammatory reactions that are induced through HMGB/RAGE receptors axis. On the other hand, heparinoid, which is low molecular weight heparin (LMWH), has anti-inflammatory effect with very low anti-coagulant activity has been used successfully in management of ALI through inhibition of neutrophil-mediated release of HMGB (Rasmuson et al 2019 ; Utsunomiya et al 2018 ). Therefore, heparin and other LMWH derivatives are effective in management of critical COVID-19 patients their antiviral and anti-inflammatory effects (Hippensteel et al 2020 ).…”

Polyphyllin I Inhibits Propionibacterium acnes-Induced IL-8 Secretion in HaCaT Cells by Downregulating the CD36/NOX1/ROS/NLRP3/IL-1β Pathway

“…ROS serves as a trigger that activates the NLRP3 inflammasome, facilitating the pathological processes. External stimuli such as a bacterial infection may trigger the activation of NLRP3 inflammasome [ 24 , 25 ], causing the release of cytokines and O 2 − effectors, which leads to chronic sterile inflammation and tissue injury [ 26 , 27 ]. If the ROS is more than their scavengers during the local inflammatory response, it results in the increasing intracellular and extracellular oxidative stress and IL-8 secretion [ 28 , 29 ], bringing about the progression of AV [ 30 , 31 ].…”

Efficacy and Safety of Mucopolysaccharide Polysulfate Cream for Non-Exudative Eczema: A Systematic Review and Meta-Analysis

“…Moreover, the mRNA expression levels of some cytokines in lesions were also significantly decreased, including IL-4, IL-6, IL-13, and IL-22 (37). MPS cream also could suppress IL-1ß production from keratinocytes by inhibiting EKR and p38 MAPK pathways (40). In this meta-analysis, the results supported that MPS cream as an add-on treatment could significantly enhance the anti-inflammatory effect of TCS or TAC-O (25,34).…”