title: Expression of matrix metalloproteinase-13 is controlled by IL-13 via PI3K/Akt3 and PKC-δ in normal human dermal fibroblasts.
abstract: IL-13, a T helper type 2 cytokine, is reported to be increased in the tissue of patients with atopic dermatitis (AD). In addition, chronic lichenified plaques in AD show thickened epidermis and dermis. We hypothesized that IL-13 is involved in tissue remodeling by altering the expression of matrix metalloproteinases (MMPs). In this study, we examined the MMP-related genes targeted by IL-13 in human dermal fibroblasts using a complementary DNA microarray. We focused on the MMP-13 gene, which was identified as one of the MMPs suppressed by IL-13. IL-13 downregulated both MMP-13 protein and mRNA expression. IL-13 suppressed MMP-13 expression more effectively in the presence of protein kinase C (PKC)-δ inhibitor, whereas IL-13 upregulated MMP-13 in the presence of inhibitors of phosphoinositide 3-kinase (PI3K)/Akt pathway or Akt3-specific small interfering RNA. Our results suggest that MMP-13 expression is negatively controlled by PI3K/Akt3 and positively regulated by PKC-δ in the presence of IL-13. Taken together, these findings indicate that IL-13 may induce the formation of thickened dermis in AD by decreasing collagen degradation. Blockade of IL-13 signaling cascades in AD patients may be a new therapeutic approach.
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Moriya
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Jinnin
authors.forename: Keitaro
authors.initials: K
authors.lastname: Yamane
authors.forename: Keishi
authors.initials: K
authors.lastname: Maruo
authors.forename: Faith C
authors.initials: FC
authors.lastname: Muchemwa
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Igata
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Makino
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukushima
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ihn
mesh_terms: D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000378:metabolism; D020405:Dermis / Q000166:cytology / Q000378:metabolism*; D015536:Down-Regulation; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
chemical_list: D018793:Interleukin-13; D003094:Collagen; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051745:Protein Kinase C-delta; D053509:Matrix Metalloproteinase 13