MIP-1 alpha, 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-1 alpha, we hypothesized that keratinocytes produce MIP-1 alpha in response to virus-associated dsRNA via TLR3. To investigate this, we examined cultured human keratinocytes for MTP-1 alpha production induced by poly(I:C), a TLR3 ligand. Poly(I:C) treatment induced MIP-1 alpha production, interestingly, poly([: C)-induced IFN-alpha and -beta production preceded MIP-1 alpha production. A neutralizing antibody for IFN-beta significantly inhibited the poly(T: C) -induced MIP-1 alpha production indicating that MIP-1 alpha production is via IFN-beta. IFN-alpha priming enhanced TLR3 expression and MIP-1 alpha 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-1 alpha production. In conclusion, normal human keratinocytes produce MIP-1 alpha in response to dsRNA via TLR3, and this production is regulated by IFN-(alpha/beta. (c) 2005 Elsevier Inc. All rights reserved.