Expression of Matrix Metalloproteinase-13 Is Controlled by IL-13 via PI3K/Akt3 and PKC-δ in Normal Human Dermal Fibroblasts

• Published in: Journal of investigative dermatology Vol. 131; no. 3; pp. 655 - 661
• Main Authors: Moriya, Chikako, Jinnin, Masatoshi, Yamane, Keitaro, Maruo, Keishi, Muchemwa, Faith C., Igata, Toshikatsu, Makino, Takamitsu, Fukushima, Satoshi, Ihn, Hironobu
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.03.2011; Nature Publishing Group
• Subjects: Biological and medical sciences; Cells, Cultured; Collagen - metabolism; Dermatitis, Atopic - metabolism; Dermatology; Dermis - cytology; Dermis - metabolism; Down-Regulation; Fibroblasts - cytology; Fibroblasts - metabolism; Humans; Interleukin-13 - metabolism; Matrix Metalloproteinase 13 - metabolism; Medical sciences; Phosphatidylinositol 3-Kinases - metabolism; Protein Kinase C-delta - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Human; Derm; Dermatology; Fibroblast; Collagenase 3
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/jid.2010.361

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.