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  Inflammation & Allergy-Drug Targets (Formerly Current Drug Targets - Inflammation & Allergy)

Volume 10 Issue 3
ISSN: 1871-5281

   All Titles

Double-Stranded RNA Induces MMP-9 Gene Expression in HaCaT Keratinocytes by Tumor Necrosis Factor-α
pp.171-179 (9) Authors: Andreas Voss, Kirsten Gescher, Andreas Hensel, Wolfgang Nacken, Claus Kerkhoff

Viral double-stranded RNA (dsRNA) and its synthetic analog poly(I:C) are recognized via multiple pathways and induce the expression of genes related to inflammation. In the present study, we demonstrate that poly(I:C) specifically induced the expression of matrix metalloproteinase-9 (MMP-9) in HaCaT keratinocytes. Studies using specific pharmacological inhibitors revealed the involvement of NF-κB, p38 MAPK, and PI-3K signal transduction pathways in poly(I:C)-induced MMP-9 gene expression. MMP-9 gene induction was sensitive toward treatment with the macrolide antibiotic bafilomycin A1, a vacuolar H+-ATPase inhibitor, and with the lysosomotropic agent chloroquine. However, cycloheximide treatment only partially blocked poly(I:C)-induced MMP-9 gene expression. Although HaCaT keratinocytes produce a number of cytokines and chemokines in response to poly(I:C), stimulation experiments revealed that exclusively TNF-α strongly promoted MMP-9 gene expression. During the antiviral response MMP-9 expression may be of importance for the tissue injury phase.

Keywords: Cytokine burst, nonviral dsRNA, organotypic skin model, secondary response gene, tissue repair, Tumor Necrosis Factor-, poly(I:C), HaCaT keratinocytes, MMP-9, Cytokine-Dependent MMP-9 Gene Expression
Affiliation: Institute of Immunology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, D-38124 Braunschweig, Germany.

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