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Heparinoid suppresses Der p‐induced IL ‐1β production by inhibiting ERK and p38 MAPK pathways in keratinocytes
Author(s) -
Utsunomiya Ryo,
Dai Xiuju,
Murakami Masamoto,
Masuda Kana,
Okazaki Hidenori,
Tsuda Teruko,
Mori Hideki,
Shiraishi Ken,
Tohyama Mikiko,
Sayama Koji
Publication year - 2018
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13685
Subject(s) - heparinoid , keratinocyte , inflammasome , inflammation , chemistry , mapk/erk pathway , epidermis (zoology) , immunology , house dust mite , biology , allergen , signal transduction , biochemistry , allergy , heparin , in vitro , anatomy
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 NLRP 3 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.