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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: NF-ýýB inducing kinase, NIK mediates cigarette smoke/TNFýý-induced histone acetylation and inflammation through differential activation of IKKs.

Authors: Chung, Sangwoon; Sundar, Isaac K; Hwang, Jae-Woong; Yull, Fiona E; Blackwell, Timothy S; Kinnula, Vuokko L; Bulger, Michael; Yao, Hongwei; Rahman, Irfan

Published In PLoS One, (2011)

Abstract: Nuclear factor (NF)-ýýB inducing kinase (NIK) is a central player in the non-canonical NF ýýB pathway, which phosphorylates IýýB kinase ýý (IKKýý) resulting in enhancement of target gene expression. We have recently shown that IKKýý responds to a variety of stimuli including oxidants and cigarette smoke (CS) regulating the histone modification in addition to its role in NF-ýýB activation. However, the primary signaling mechanism linking CS-mediated oxidative stress and TNFýý with histone acetylation and pro-inflammatory gene transcription is not well understood. We hypothesized that CS and TNFýý increase NIK levels causing phosphorylation of IKKýý, which leads to histone acetylation.To test this hypothesis, we investigated whether NIK mediates effects of CS and TNFýý on histone acetylation in human lung epithelial cells in vitro and in lungs of mouse exposed to CS in vivo. CS increased the phosphorylation levels of IKKýý/NIK in lung epithelial cells and mouse lungs. NIK is accumulated in the nuclear compartment, and is recruited to the promoters of pro-inflammatory genes, to induce posttranslational acetylation of histones in response to CS and TNFýý. Cells in which NIK is knocked down using siRNA showed partial attenuation of CSE- and TNFýý-induced acetylation of histone H3 on pro-inflammatory gene promoters. Additional study to determine the role of IKKýý/NF-ýýB pathway in CS-induced histone acetylation suggests that the canonical pathway does not play a role in histone acetylation particularly in response to CS in mouse lungs.Overall, our findings provide a novel role for NIK in CS- and TNFýý-induced histone acetylation, especially on histone H3K9.

PubMed ID: 21887257 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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