Cigarette smoke extract stimulates mmp-2 production in nasal fibroblasts via ros/pi3k, akt, and nf-κb signaling pathways

Joo Hoo Park, Jae Min Shin, Hyun Woo Yang, Tae Hoon Kim, Seung Hoon Lee, Heung Man Lee, Jae Gu Cho, Il Ho Park

Research output: Contribution to journalArticle

Abstract

Cigarette smoke exposure has been shown to be associated with chronic rhinosinusitis and tissue remodeling. The present study aimed to investigate the effects of cigarette smoke extract (CSE) on matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) production in nasal fibroblasts and to determine the underlying molecular mechanisms. Primary nasal fibroblasts from six patients were isolated and cultured. After the exposure of fibroblasts to CSE, the expression levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured by real-time PCR, ELISA, and immunofluorescence staining. The enzymatic activities of MMP-2 and MMP-9 were measured by gelatin zymography. Reactive oxygen species (ROS) production was analyzed using dichloro-dihydro-fluorescein diacetate and Amplex Red assays. PI3K/Akt phosphorylation and NF-κB activation were determined by Western blotting and luciferase assay. CSE significantly increased MMP-2 expression and inhibited TIMP-2 expression but did not affect MMP-9 and TIMP-1 expression. Furthermore, CSE significantly induced ROS production. However, treatment with ROS scavengers, specific PI3K/Akt inhibitors, NF-κB inhibitor, and glucocorticosteroids significantly decreased MMP-2 expression and increased TIMP-2 expression. Our results suggest that steroids inhibit CSE-regulated MMP-2 and TIMP-2 production and activation through the ROS/ PI3K, Akt, and NF-κB signaling pathways in nasal fibroblasts. CSE may contribute to the pathogenesis of chronic rhinosinusitis by regulating MMP-2 and TIMP-2 expression.

Original languageEnglish
Article number739
Pages (from-to)1-14
Number of pages14
JournalAntioxidants
Volume9
Issue number8
DOIs
Publication statusPublished - 2020 Aug

Keywords

  • Cigarette smoke extract
  • Matrix metalloproteinase
  • Nasal fibroblasts
  • Steroids
  • Tissue inhibitor of metalloproteinases

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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