title: Bone marrow mononuclear cells up-regulate toll-like receptor expression and produce inflammatory mediators in response to cigarette smoke extract.
abstract: Several reports link cigarette smoking with leukemia. However, the effects of cigarette smoke extract (CSE) on bone marrow hematopoiesis remain unknown. The objective of this study was to elucidate the direct effects of cigarette smoke on human bone marrow hematopoiesis and characterize the inflammatory process known to result from cigarette smoking. Bone marrow mononuclear cells (BMCs) from healthy individuals when exposed to CSE had significantly diminished CFU-E, BFU-E and CFU-GM. We found increased nuclear translocation of the NF-κB p65 subunit and, independently, enhanced activation of AKT and ERK1/2. Exposure of BMCs to CSE induced IL-8 and TGF-β1 production, which was dependent on NF-κB and ERK1/2, but not on AKT. CSE treatment had no effect on the release of TNF-α, IL-10, or VEGF. Finally, CSE also had a significant induction of TLR2, TLR3 and TLR4, out of which, the up-regulation of TLR2 and TLR3 was found to be dependent on ERK1/2 and NF-κB activation, but not AKT. These results indicate that CSE profoundly inhibits the growth of erythroid and granulocyte-macrophage progenitors in the bone marrow. Further, CSE modulates NF-κB- and ERK1/2-dependent responses, suggesting that cigarette smoking may impair bone marrow hematopoiesis in vivo as well as induce inflammation, two processes that proceed malignant transformation.
authors: Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America.
authors: Junmin
authors: J
authors: Zhou
authors: Erika A
authors: EA
authors: Eksioglu
authors: Nicole R
authors: NR
authors: Fortenbery
authors: Xianghong
authors: X
authors: Chen
authors: Huaquan
authors: H
authors: Wang
authors: Pearlie K
authors: PK
authors: Epling-Burnette
authors: Julie Y
authors: JY
authors: Djeu
authors: Sheng
authors: S
authors: Wei
mesh_terms: D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects*; D051193:Toll-Like Receptors / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016209:Interleukin-8; D051193:Toll-Like Receptors; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10