IL-17A versus IL-17F induced intracellular signal transduction pathways and modulation by IL-17RA and IL-17RC RNA interference in AGS gastric adenocarcinoma cells.

Abstract:

:Inflammatory processes are implicated in gastric cancer development. In contrast, the role of inflammation and proinflammatory cytokines in established cancer remains to be clarified. We investigated the contribution of IL-17A versus IL-17F-mediated intracellular signalling pathways in human gastric adenocarcinoma AGS cells. IL-8 secretion was evaluated by ELISA, mitogen-activated protein kinase (MAPK)(4) by Western blotting, and activator protein 1(AP-1) and nuclear factor kappa B (NFkappaB) by TransAM transcription factor assay or qRT-PCR. IL-17RA and IL-17RC inhibition were achieved by small interfering RNA (siRNA). IL-17A significantly induced activation of all three MAPK (ERK, p38 and JNK) and downstream transcription factors AP-1 and p65 NFkappaB. IL-17F was less potent but induced a significant activation of p65 NFkappaB. Consistently, IL-17A was more potent to induce IL-8 secretion than IL-17F. Inhibition of either IL-17RA or IL-17RC expression via siRNA led to near complete abrogation of IL-17A-mediated c-Jun and p65 activation. These data suggest that in gastric cancer, absence of either IL-17RA or IL-17RC can inhibit IL-17 responsiveness. Conversely, downstream of IL-17R binding, IL-17A and IL-17F induce key signal transduction pathways implicated in inflammation and carcinogenesis. IL-17A, and possibly IL-17F, may contribute to amplification and persistence of inflammatory processes implicated in inflammation-associated cancer.

journal_name

Cytokine

journal_title

Cytokine

authors

Zhou Y,Toh ML,Zrioual S,Miossec P

doi

10.1016/j.cyto.2007.06.002

subject

Has Abstract

pub_date

2007-06-01 00:00:00

pages

157-64

issue

3

eissn

1043-4666

issn

1096-0023

pii

S1043-4666(07)00152-4

journal_volume

38

pub_type

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