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PLoS One. 2014 Jun 6;9(6):e96678. doi: 10.1371/journal.pone.0096678. eCollection 2014.

Interleukin 17A promotes gastric cancer invasiveness via NF-κB mediated matrix metalloproteinases 2 and 9 expression.

Author information

1
Department of Obstetrics and Gynecology, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
2
Department of General Surgery, XIAN XD GROUP Hospital, Xi'an, Shaanxi, P. R. China.
3
Department 5 of rheumatology, the fifth hospital of Xi'an city, Xi'an, Shaanxi, P. R. China.

Abstract

Interleukin 17A (IL-17A), as a pro-inflammatory cytokine, is involved in pathology of inflammatory diseases and tumor microenvironment. The aim of this study is to investigate the effect of IL-17A on the invasiveness of gastric cancer (GC). In the study, we found that IL-17A could promote the migration and invasion of GC cells. Furthermore, after treated with IL-17A, the expressions and activities of matrix metalloproteinase 2 (MMP-2) and MMP-9 were upregulated, while the expressions of TIMP-1 and TIMP-2 were downregulated. Moreover, the nuclear/overall fractions of p65 and p50 were dramatically elevated by IL-17A. Pretreatment with helenalin, a nuclear factor-κB (NF-κB) inhibitor, was proved to abolish the promoting effect of IL-17A on the invasion ability of GC cells and upregulation of MMP-2 and MMP-9. In conclusion, our findings illustrated that IL-17A could promote the invasion of GC cells by activating NF-κB pathway, and subsequently upregulating the expression of MMP-2 and MMP-9. These results may lead to the identification of new diagnostic markers and therapeutic targets of GC.

PMID:
24905806
PMCID:
PMC4048176
DOI:
10.1371/journal.pone.0096678
[Indexed for MEDLINE]
Free PMC Article

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