Induction of the Matrix Metalloproteinase 13 Gene in Bronchial Epithelial Cells by Interferon and Identification of its Novel Functional Polymorphism

Yoichi Mashimo, Mika Sakurai-Yageta, Misa Watanabe, Takayasu Arima, Yoshinori Morita, Yuzaburo Inoue, Kazuki Sato, Toshiyuki Nishimuta, Shuichi Suzuki, Hiroko Watanabe, Akira Hoshioka, Minako Tomiita, Akiko Yamaide, Yoichi Kohno, Yoshitaka Okamoto, Naoki Shimojo, Akira Hata, Yoichi Suzuki

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Matrix metalloproteinases (MMPs) are a class of extra-cellular and membrane-bound proteases involved in a wide array of physiological and pathological processes including tissue remodeling, inflammation, and cytokine secretion and activation. MMP-13 has been shown to be involved in lung diseases such as acute lung injury, viral infections, and chronic obstructive pulmonary disease; however, the molecular pathogenesis of MMP-13 in these conditions is not well understood. In this study, we investigated the mechanisms and roles of MMP-13 secretion in human small airway epithelial cells (SAECs) and functional polymorphisms of the MMP13 gene. Polyinosinic–polycytidylic acid (poly(I:C)) and interferon β (IFN-β) stimulated the secretion of MMP-13 from SAECs by more than several hundred-fold. Stimulation of the secretion by poly(I:C) was abolished by SB304680 (p38 inhibitor), LY294002 (PI3K inhibitor), Janus kinase (JAK) inhibitor I, RNA-activated protein kinase (PKR) inhibitor, and Bay 11-7082 (NF-κB inhibitor), while stimulation by IFN-β was inhibited by all except Bay 11-7082. These data suggested that the secretion of MMP-13 was mediated through IFN receptor pathways independently of nuclear factor kappa B (NF-κB) and that poly(I:C) stimulated IFN secretion in an NF-κB-dependent manner from SAECs, leading to IFN-stimulated MMP-13 secretion. Chemical MMP-13 inhibitors and MMP-13 small interfering RNA (siRNA) inhibited IFN-stimulated secretion of interferon gamma-inducible protein 10 (IP-10) and regulated on activation, normal T-cell expressed and secreted (RANTES), suggesting that MMP-13 is involved in the secretion of these virus-induced proinflammatory chemokines. We identified a novel functional polymorphism in the promoter region of the MMP13 gene. The MMP13 gene may play important roles in defense mechanisms of airway epithelial cells.

Original languageEnglish
Pages (from-to)949-962
Number of pages14
JournalInflammation
Volume39
Issue number3
DOIs
Publication statusPublished - 2016 Jun 1

Keywords

  • airway epithelial cell
  • collagenase 3
  • gene expression
  • infection
  • interferron beta
  • matrix metalloproteinase 13
  • polymorphism

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Mashimo, Y., Sakurai-Yageta, M., Watanabe, M., Arima, T., Morita, Y., Inoue, Y., Sato, K., Nishimuta, T., Suzuki, S., Watanabe, H., Hoshioka, A., Tomiita, M., Yamaide, A., Kohno, Y., Okamoto, Y., Shimojo, N., Hata, A., & Suzuki, Y. (2016). Induction of the Matrix Metalloproteinase 13 Gene in Bronchial Epithelial Cells by Interferon and Identification of its Novel Functional Polymorphism. Inflammation, 39(3), 949-962. https://doi.org/10.1007/s10753-015-0291-1