Shingles Research Today is a free monthly online journal that collates and summarizes the latest research about Shingles, including details on symptoms, treatment, causes, virus.

dsRNA-mediated innate immunity of epidermal keratinocytes.

Tohyama M, Dai X, Sayama K, Yamasaki K, Shirakata Y, Hanakawa Y, Tokumaru S, Yahata Y, Yang L, Nagai H, Takashima A, Hashimoto K

Department of Dermatology, Ehime University School of Medicine, Shitsukawa, Toon-city, Ehime 791-0295, Japan.

MIP-1alpha, a CC chemokine, recruits monocytes, natural killer cells, lymphocytes, and neutrophils, and plays a critical role in viral infection. Since, the lesional epidermis of herpes zoster expressed MIP-1alpha, we hypothesized that keratinocytes produce MIP-1alpha in response to virus-associated dsRNA via TLR3. To investigate this, we examined cultured human keratinocytes for MIP-1alpha production induced by poly(I:C), a TLR3 ligand. Poly(I:C) treatment induced MIP-1alpha production, interestingly, poly(I:C)-induced IFN-alpha and -beta production preceded MIP-1alpha production. A neutralizing antibody for IFN-beta significantly inhibited the poly(I:C)-induced MIP-1alpha production indicating that MIP-1alpha production is via IFN-beta. IFN-alpha priming enhanced TLR3 expression and MIP-1alpha production in poly(I:C)-treated keratinocytes. This suggests that IFN-alpha enhanced the TLR3 expression and reinforced the response of keratinocytes to poly(I:C), which resulted in an increase in MIP-1alpha production. In conclusion, normal human keratinocytes produce MIP-1alpha in response to dsRNA via TLR3, and this production is regulated by IFN-alpha/beta.

Published 15 August 2005 in Biochem Biophys Res Commun, 335(2): 505-11.
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