CD14 MEDIATED ENDOGENOUS TNF-ALPHA RELEASE IN HL-60 AML CELLS - A POTENTIAL MODEL FOR CD14 MEDIATED ENDOGENOUS CYTOKINE RELEASE IN THE TREATMENT OF AML

In previous studies, HL60 AML cells treated with tumor necrosis factor -alpha (TNF), interferon-gamma (IFN), and lipopolysaccharides (LPS) di splayed decreased growth and viability, enhanced monocytic pathway dif ferentiation and endogenous TNF release. Endogenous TNF release by LPS /TNF/IFN treated HL60 cells was postulated to play a role with the abo ve findings. In these studies, HL60 cells expressed CD14 when treated with TNF, IFN, and LPS. CD14 mediates TNF release in monocytes/macroph ages in response to binding of LPS with LPS binding protein (LBP). CD1 4 was not expressed in either untreated or LPS only treated HL60 cells . CD14 expression was present and greater with HL60 cells cultured wit h LPS/TNF/IFN vs TNF/IFN (47.47% vs 9.07% positive, respectively) sugg esting synergism for LPS in CD14 induction. CD14 expression was associ ated with endogenous TNF release, and with significantly higher levels by HL60 cells treated with LPS/TNF/IFN vs TNF/IFN (p < 0.001). Additi on of anti-CD14 antibody significantly reduced release of TNF in TNF/I FN (p < 0.001) and LPS/TNF/IFN (p = 0.0013) treated cells. KG1 and U93 7 AML cells treated with LPS, TNF, and IFN did not express CD14, nor r elease TNF. A model for inducing release of endogenous growth inhibito ry cytokines by CD14 bearing AML cells is proposed as an approach to A ML therapy.