Biomol Ther.  2018 Jul;26(4):417-423. 10.4062/biomolther.2017.167.

IL-1 Receptor Antagonist Reduced Chemical-Induced Keratinocyte Apoptosis through Antagonism to IL-1α/IL-1β

• Lee H
• Cheong KA
• Kim JY
• Kim NH
• Noh M
• Lee AY

• KMID: 2420393
• DOI: http://doi.org/10.4062/biomolther.2017.167

Abstract

Extracellular interleukin 1 alpha (IL-1α) released from keratinocytes is one of the endpoints for in vitro assessments of skin irritancy. Although cells dying via primary skin irritation undergo apoptosis as well as necrosis, IL-1α is not released in apoptotic cells. On the other hand, active secretion has been identified in interleukin-1 receptor antagonist (IL-1ra), which was discovered to be a common, upregulated, differentially-expressed gene in a microarray analysis performed with keratinocytes treated using cytotoxic doses of chemicals. This study examined whether and how IL-1ra, particularly extracellularly released IL-1ra, was involved in chemically-induced keratinocyte cytotoxicity and skin irritation. Primary cultured normal adult skin keratinocytes were treated with cytotoxic doses of chemicals (hydroquinone, retinoic acid, sodium lauryl sulfate, or urshiol) with or without recombinant IL-1ra treatment. Mouse skin was administered irritant concentrations of hydroquinone or retinoic acid. IL-1ra (mRNA and/or intracellular/extracellularly released protein) levels increased in the chemically treated cultured keratinocytes with IL-1α and IL-1β mRNAs and in the chemically exposed epidermis of the mouse skin. Recombinant IL-1ra treatment significantly reduced the chemically-induced apoptotic death and intracellular/extracellularly released IL-1α and IL-1β in keratinocytes. Collectively, extracellular IL-1ra released from keratinocytes could be a compensatory mechanism to reduce the chemically-induced keratinocyte apoptosis by antagonism to IL-1α and IL-1β, suggesting potential applications to predict skin irritation.

Keyword

IL-1ra; Keratinocyte apoptosis; Skin irritation

MeSH Terms

Adult
Animals
Apoptosis*
Epidermis
Hand
Humans
In Vitro Techniques
Interleukin 1 Receptor Antagonist Protein
Interleukin-1*
Interleukin-1alpha
Keratinocytes*
Mice
Microarray Analysis
Necrosis
RNA, Messenger
Skin
Sodium Dodecyl Sulfate
Tretinoin
Interleukin 1 Receptor Antagonist Protein
Interleukin-1
Interleukin-1alpha
RNA, Messenger
Sodium Dodecyl Sulfate
Tretinoin