Mite allergen is a danger signal for the skin via activation of inflammasome in keratinocytes - 10/08/11
, Mikiko Tohyama, MD, PhD, Yuji Shirakata, MD, PhD, Yasushi Hanakawa, MD, PhD, Sho Tokumaru, MD, PhD, Lujun Yang, MD, PhD, Satoshi Hirakawa, MD, PhD, Koji Hashimoto, MD, PhD
Reprint requests: Koji Sayama, MD, PhD, Department of Dermatology, Ehime University Graduate School of Medicine, Ehime 791-0295, Japan.Abstract |
Background |
Atopic dermatitis (AD) is a chronic inflammatory skin disorder caused by multiple factors. Among them, house dust mite (HDM) allergens are important in the development of AD. In airway allergy, HDM allergens activate innate immunity. However, information regarding the activation of innate immunity by HDM allergens in the skin is limited.
Objectives |
The inflammasome is a key regulator of pathogen recognition and inflammation. We investigated whether HDM allergens activate the inflammasome in epidermal keratinocytes.
Methods |
Keratinocytes were stimulated with Dermatophagoides pteronyssinus, and the activation of caspase-1 and secretion of IL-1β and IL-18 were examined. Formation of the inflammasome was studied by analyzing the subcellular distributions of inflammasome proteins. The importance of specific inflammasome proteins was studied by knocking down their expression through transfection of keratinocytes with lentiviral particles carrying short hairpin RNAs (shRNAs).
Results |
D pteronyssinus activated caspase-1 and induced caspase-1–dependent release of IL-1β and IL-18 from keratinocytes. Moreover, D pteronyssinus stimulated assembly of the inflammasome by recruiting apoptosis-associated specklike protein containing a caspase-recruitment domain (ASC), caspase-1, and nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin-domain containing 3 (NLRP3) to the perinuclear region. Finally, infection with lentiviral particles carrying ASC, caspase-1, or NLRP3 shRNAs suppressed the release of IL-1β and IL-18 from the keratinocytes. Activation of the NLRP3 inflammasome by D pteronyssinus was dependent on cysteine protease activity.
Conclusion |
House dust mite allergens are danger signals for the skin. In addition, HDM-induced activation of the NLRP3 inflammasome may play a pivotal role in the pathogenesis of AD.
Le texte complet de cet article est disponible en PDF.Key words : Keratinocytes, house dust mite, caspase-1, IL-1β, IL-18, NLRP3, inflammasome, Dermatophagoides pteronyssinus, Der p 1
Abbreviations used : AD, ASC, E-64, HDM, HMGB1, NF-κB, NLR, NLRP, PAR2, PMA, PolyI:C, shRNAs, TLR, zVAD, zYVAD
Plan
| Supported by grants from the Ministries of Health, Labor, and Welfare and Education, Culture, Sports, Science and Technology, Japan. |
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| Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest. |
Vol 127 - N° 3
P. 806 - mars 2011 Retour au numéro
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