dsRNA-mediated innate immunity of epidermal keratinocytes.
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.
Tohyama
Mikiko
M
Department of Dermatology, Ehime University School of Medicine, Shitsukawa, Toon-city, Ehime 791-0295, Japan.
Dai
Xiuju
X
Sayama
Koji
K
Yamasaki
Kenshi
K
Shirakata
Yuji
Y
Hanakawa
Yasushi
Y
Tokumaru
Sho
S
Yahata
Yoko
Y
Yang
Lujun
L
Nagai
Hiroshi
H
Takashima
Akira
A
Hashimoto
Koji
K
D002478:Cells, Cultured / Q000166:cytology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D004797:Enzyme-Linked Immunosorbent Assay; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D006562:Herpes Zoster / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate; D007150:Immunohistochemistry; D016899:Interferon-beta / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D008024:Ligands; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008954:Models, Biological; D012313:RNA / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism; D013997:Time Factors; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D008024:Ligands; D019402:Macrophage Inflammatory Proteins; D008562:Membrane Glycoproteins; D012330:RNA, Double-Stranded; D011956:Receptors, Cell Surface; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; D012313:RNA; D016899:Interferon-beta