Cigarette Smoke Exposure Alters mSin3a and Mi-2alpha/beta Expression; implications in the control of pro-inflammatory gene transcription and glucocorticoid function.

Journal of Inflammation
J A MarwickP Kirkham

Abstract

The key co-repressor complex components HDAC-2, Mi-2alpha/beta and mSin3a are all critical to the regulation of gene transcription. HDAC-2 function is impaired by oxidative stress in a PI3Kdelta dependant manner which may be involved in the chronic glucocorticoid insensitive inflammation in the lungs of COPD patients. However, the impact of cigarette smoke exposure on the expression of mSin3a and Mi2alpha/beta and their role in glucocorticoid responsiveness is unknown. Wild type, PI3Kgamma knock-out (PI3Kgamma-/-) and PI3K kinase dead knock-in (PI3KdeltaD910/A910) transgenic mice were exposed to cigarette smoke for 3 days and the expression levels of the co-repressor complex components HDAC-2, mSin3a, Mi-2alpha and Mi-2beta and HDAC-2 activity in the lungs were assessed. Cigarette smoke exposure impaired glucocorticoid function and reduced HDAC-2 activity which was protected in the PI3KdeltaD910/A910 mice. Both mSin3a and Mi-2alpha protein expression was reduced in smoke-exposed mice. Budesonide alone protected mSin3a protein expression with no additional effect seen with abrogation of PI3Kgamma/delta activity, however Mi-2alpha, but not Mi-2beta, expression was protected in both PI3KdeltaD910/A910 and PI3Kgamma-/- budesonide-t...Continue Reading

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Methods Mentioned

BETA
acetylation
immunoprecipitation

Software Mentioned

GraphPad Prism

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