Activation of TLR3 in keratinocytes increases expression of genes involved in formation of the epidermis, lipid accumulation, and epidermal organelles.
Injury to the skin, and the subsequent release of noncoding double-stranded RNA (dsRNA) from necrotic keratinocytes, has been identified as an endogenous activator of Toll-like receptor 3 (TLR3). As changes in keratinocyte growth and differentiation follow injury, we hypothesized that TLR3 might trigger some elements of the barrier repair program in keratinocytes. dsRNA was observed to induce TLR3-dependent increases in human keratinocyte mRNA abundance for ABCA12 (ATP-binding cassette, sub-family A, member 12), glucocerebrosidase, acid sphingomyelinase, and transglutaminase 1. Additionally, treatment with dsRNA resulted in increases in sphingomyelin and morphologic changes including increased epidermal lipid staining by Oil Red O and TLR3-dependent increases in lamellar bodies and keratohyalin granules. These observations show that dsRNA can stimulate some events in keratinocytes that are important for skin barrier repair and maintenance.
Division of Dermatology, University of California, San Diego, San Diego, California 92093-0869, USA.
Andrew W
AW
Borkowski
Kyungho
K
Park
Yoshikazu
Y
Uchida
Richard L
RL
Gallo
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000293:injuries / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D050356:Lipid Metabolism / Q000502:physiology*; D015388:Organelles / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome; D014945:Wound Healing / Q000502:physiology*
C473801:ABCA12 protein, human; D018528:ATP-Binding Cassette Transporters; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D011070:Poly I-C