tailieunhanh - Báo cáo y học: " Histone deacetylase inhibitors induce apoptosis in human eosinophils and neutrophils"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Histone deacetylase inhibitors induce apoptosis in human eosinophils and neutrophils. | Kankaanranta et al. Journal of Inflammation 2010 7 9 http content 7 1 9 JOURNAL OF INFLAMMATION RESEARCH Open Access Histone deacetylase inhibitors induce apoptosis in human eosinophils and neutrophils Hannu Kankaanranta1 2 Mirkka Janka-Junttila 1 Pinja Ilmarinen-Salo1 Kazuhiro Ito3 Ulla Jalonen1 Misako Ito3 Ian M Adcock3 Eeva Moilanen1 Xianzhi Zhang1 Abstract Background Granulocytes are important in the pathogenesis of several inflammatory diseases. Apoptosis is pivotal in the resolution of inflammation. Apoptosis in malignant cells is induced by histone deacetylase HDAC inhibitors whereas HDAC inhibitors do not usually induce apoptosis in non-malignant cells. The aim of the present study was to explore the effects of HDAC inhibitors on apoptosis in human eosinophils and neutrophils. Methods Apoptosis was assessed by relative DNA fragmentation assay annexin-V binding and morphologic analysis. HDAC activity in nuclear extracts was measured with a nonisotopic assay. HDAC expression was measured by real-time PCR. Results A HDAC inhibitor Trichostatin A TSA induced apoptosis in the presence of survival-prolonging cytokines interleukin-5 and granulocyte-macrophage colony stimulating factor GM-CSF in eosinophils and neutrophils. TSA enhanced constitutive eosinophil and neutrophil apoptosis. Similar effects were seen with a structurally dissimilar HDAC inhibitor apicidin. TSA showed additive effect on the glucocorticoid-induced eosinophil apoptosis but antagonized glucocorticoid-induced neutrophil survival. Eosinophils and neutrophils expressed all HDACs at the mRNA level except that HDAC5 and HDAC11 mRNA expression was very low in both cell types HDAC8 mRNA was very low in neutrophils and HDAC9 mRNA low in eosinophils. TSA reduced eosinophil and neutrophil nuclear HDAC activities by 50-60 suggesting a non-histone target. However TSA did not increase the acetylation of a non-histone target NF-kB p65. c-jun-N-terminal kinase and caspases 3 and