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- Title
Expression of Matrix Metalloproteinase-13 Is Controlled by IL-13 via PI3K/Akt3 and PKC-δ in Normal Human Dermal Fibroblasts.
- Authors
Moriya, Chikako; Jinnin, Masatoshi; Yamane, Keitaro; Maruo, Keishi; Muchemwa, Faith C; Igata, Toshikatsu; Makino, Takamitsu; Fukushima, Satoshi; Ihn, Hironobu
- 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.
- Subjects
METALLOPROTEINASES; FIBROBLASTS; CYTOKINES; ATOPIC dermatitis treatment; TISSUE remodeling; DNA microarrays; PROTEIN kinases; MESSENGER RNA
- Publication
Journal of Investigative Dermatology, 2011, Vol 131, Issue 3, p655
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1038/jid.2010.361