Differential induction of apoptosis by LPS and taxol in monocytic cells.
Numerous microbial as well as other stimulants including lipopolysaccharide and taxol can activate TLR4, and elicit diverse downstream signaling events including cytokine gene expression and cell growth regulation. With a mechanism not completely understood, different TLR4 stimulants induce distinct cellular responses. Our present studies showed that taxol, not LPS, induced cell apoptosis in human monocytic THP-1 cells, as indicated by PARP cleavage, as well as bcl-2 phosphorylation. Pretreatment of cells with LPS abolished subsequent taxol effect, suggesting that certain signaling components involved in taxol-mediated apoptosis were disrupted by LPS pretreatment. Since the decrease in IRAK-1 level closely accompanies prolonged LPS treatment in monocytic cells, we investigated the IRAK-1 status upon various taxol and LPS challenges. We observed that only LPS, not taxol, caused dramatic decrease in IRAK-1 protein levels. Using splenic macrophages harvested from IRAK-1 knockout and control mice, we further demonstrated that the presence of IRAK-1 is required for taxol-induced PARP cleavage.
Li
Tao
T
Section of Molecular Medicine, Department of Medicine, Wake Forest, University School of Medicine, Winston Salem, NC 27157, USA.
Hu
Jean
J
Thomas
James A
JA
Li
Liwu
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D015153:Blotting, Western; D002460:Cell Line; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism
D008070:Lipopolysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D017472:Receptors, Interleukin-1; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases; D017239:Paclitaxel