NF-κB Inducing Kinase, NIK Mediates Cigarette Smoke/TNFα-Induced Histone Acetylation and Inflammation through Differential Activation of IKKs
2011

NIK Regulates Histone Acetylation in Response to Cigarette Smoke and TNFα

Sample size: 37 publication 10 minutes Evidence: moderate

Author Information

Author(s): Chung Sangwoon, Sundar Isaac K., Hwang Jae-Woong, Yull Fiona E., Blackwell Timothy S., Kinnula Vuokko L., Bulger Michael, Yao Hongwei, Rahman Irfan

Primary Institution: University of Rochester Medical Center

Hypothesis

CS and TNFα increase NIK levels causing phosphorylation of IKKα, which leads to histone acetylation.

Conclusion

NIK plays a novel role in mediating cigarette smoke and TNFα-induced histone acetylation, particularly on histone H3K9.

Supporting Evidence

  • Cigarette smoke exposure increased NIK levels in human lung epithelial cells.
  • NIK was recruited to the promoters of pro-inflammatory genes in response to cigarette smoke.
  • Histone acetylation was significantly reduced in cells with NIK knockdown.
  • Patients with COPD showed increased levels of NIK and phosphorylated IKKα in lung tissues.
  • NIK mediates the effects of cigarette smoke on histone modifications.

Takeaway

When people smoke, a protein called NIK helps change how certain genes are turned on, which can lead to lung problems.

Methodology

The study used human lung epithelial cells and mouse models to investigate the effects of cigarette smoke and TNFα on histone acetylation and NIK activation.

Potential Biases

Potential biases may arise from the selection of animal models and the specific conditions under which experiments were conducted.

Limitations

The study primarily focused on in vitro and in vivo models, which may not fully replicate human responses.

Participant Demographics

The study included 37 subjects: 10 life-long non-smokers, 10 current smokers with normal lung function, and 9 patients with COPD.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0023488

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