tailieunhanh - Báo cáo y học: "Cigarette Smoke Exposure Alters mSin3a and Mi-2α/β Expression; implications in the control of pro-inflammatory gene transcription and glucocorticoid function"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Cigarette Smoke Exposure Alters mSin3a and Mi-2α/β Expression; implications in the control of pro-inflammatory gene transcription and glucocorticoid function. | Marwick et al. Journal of Inflammation 2010 7 33 http content 7 1 33 JOURNAL OF INFLAMMATION RESEARCH Open Access Cigarette Smoke Exposure Alters mSin3a and Mi-2a p Expression implications in the control of pro-inflammatory gene transcription and glucocorticoid function John A Marwick 1 2 Christopher S Stevenson3 Kian Fan Chung1 Ian M Adcock1 and Paul A Kirkham 1 2 Abstract Background The key co-repressor complex components HDAC-2 Mi-2a p and mSin3a are all critical to the regulation of gene transcription. HDAC-2 function is impaired by oxidative stress in a PI3KỖ 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 Mi2a p and their role in glucocorticoid responsiveness is unknown. Methods Wild type PI3Ky knock-out PI3Ky- - and PI3K kinase dead knock-in PI3KỖD910 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-2a and MÍ-2P and HDAC-2 activity in the lungs were assessed. Results Cigarette smoke exposure impaired glucocorticoid function and reduced HDAC-2 activity which was protected in the PI3KỖD910 A910 mice. Both mSin3a and Mi-2a protein expression was reduced in smoke-exposed mice. Budesonide alone protected mSin3a protein expression with no additional effect seen with abrogation of PI3Ky 0 activity however Mi-2a but not MÍ-2P expression was protected in both PI3KỖD910 A910 and PI3Ky- - budesonide-treated smoke-exposed mice. The restoration of glucocorticoid function coincided with the protection of both HDAC activity and mSin3a and Mi-2a protein expression. Conclusions Cigarette smoke exposure induced glucocorticoid insensitivity and alters co-repressor activity and expression which is prevented by blockade of PI3K signaling with glucocorticoid treatment. Inhibition of PI3KỖ signalling in