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: Chikako Moriya, Masatoshi Jinnin, Keitaro Yamane, Keishi Maruo, Faith C Muchemwa, Toshikatsu Igata, Takamitsu Makino, Satoshi Fukushima, Hironobu Ihn
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 131 Issue 3 Pg. 655-61 (Mar 2011) ISSN: 1523-1747 [Electronic] United States
• PMID: 21191416 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-13
• Collagen
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Protein Kinase C-delta
• Matrix Metalloproteinase 13

Topics

• Cells, Cultured
• Collagen (metabolism)
• Dermatitis, Atopic (metabolism)
• Dermis (cytology, metabolism)
• Down-Regulation
• Fibroblasts (cytology, metabolism)
• Humans
• Interleukin-13 (metabolism)
• Matrix Metalloproteinase 13 (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Protein Kinase C-delta (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)