Lentivirus-mediated ADAM17 RNA interference inhibited interleukin-8 expression via EGFR signaling in lung epithelial cells.

Abstract:

:Interleukin (IL)-8 and neutrophil inflammation play a vital role in the pathogenesis of chronic inflammatory airway diseases. A disintegrin and metalloproteinase 17 (ADAM17) cleaves ectodomains of various transmembrane proteins and is an important regulator of almost every cellular event. The aim of this work was to investigate the roles of epidermal growth factor receptor (EGFR) signaling and ADAM17 in IL-8 expression induced by lipopolysaccharide (LPS) in A549 lung epithelial cells. In the present study, we found that transforming growth factor-α (TGF-α)-neutralizing Ab, EGFR-neutralizing Ab, and AG1478 significantly inhibited the phosphorylation of EGFR and IL-8 production induced by LPS. Lentivirus-mediated ADAM-17 RNA interference markedly inhibited ADAM-17 expression, the release of TGF-α, and the phosphorylation of EGFR and IL-8 expression. The results demonstrated that lentivirus-mediated RNA interference targeting ADAM17 suppressed IL-8 expression induced by LPS via inhibiting EGFR signaling, and ADAM17-EGFR signaling cascade mediated IL-8 production induced by LPS in lung epithelial cells.

journal_name

Inflammation

journal_title

Inflammation

authors

Li Y,Yan J,Xu W,Wang H,Xia Y

doi

10.1007/s10753-011-9386-5

subject

Has Abstract

pub_date

2012-06-01 00:00:00

pages

850-8

issue

3

eissn

0360-3997

issn

1573-2576

journal_volume

35

pub_type

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