کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2133939 | 1087439 | 2015 | 5 صفحه PDF | دانلود رایگان |
• Inhibitors of p38 MAPK reduced the production of TNF-α in monocytes of FANCA
• Inhibitors of p38 MAPK improve the growth of erythroid progenitor cells
• BIRB796 improves colony growth of MNCs, but not CD34+ cells demonstrating p38 activation in marrow accessory cells
Bone marrow failure in Fanconi anemia (FA) has been linked in part to overproduction of inflammatory cytokines, to which FA stem and progenitor cells are hypersensitive. In cell lines and murine models p38 mitogen-activated protein kinase (MAPK)-dependent tumor necrosis factor α (TNF-α) overexpression can be induced by the Toll-like receptors (TLRs) 4 and 7/8 ligands Lipopolysaccharide (LPS) and R848. Ex vivo exposure of FA stem cells to TNF-α suppresses their replication and selects preleukemic clones. Here we show that inhibition of p38 MAPK also reduces TLR4 and 7/8-mediated TNF-α production in primary human
Journal: - Volume 43, Issue 4, April 2015, Pages 295–299